Modulatory Role of Garlic (Allium Sativum) Extract against Cisplatin- Induced Nephrotoxicity in Female Albino Rats and their Offspring

Modulatory Role of Garlic (Allium Sativum) Extract against Cisplatin- Induced Nephrotoxicity in Female Albino Rats and their Offspring | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Modulatory Role of Garlic (Allium Sativum) Extract against Cisplatin- Induced Nephrotoxicity in Female Albino Rats and their Offspring Abd El-Fattah El-Beltagy, Gamal Mohamed, Mohammed A Akeel, Karoline K. Abdelaziz, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1295740/v2 This work is licensed under a CC BY 4.0 License Status: Under Review Version 2 posted 6 You are reading this latest preprint version Show more versions Abstract Background: Cisplatin (CP) is one of the most powerful chemotherapeutic drugs that widely utilized in the treatment of several malignancies .However, in the late era; its use has been limited because of its hazardous health drawbacks. Previous researches confirmed that CP has severe deleterious side effects on pregnant mothers and their fetuses .Garlic ( Allium sativum ) extract has been claimed to exhibit potent antioxidative and free radical scavenging abilities in various disease conditions. Aim: The goal of the current investigation was to throw light on the CP-induced nephrotoxic effects in pregnant albino rats and their offspring and to clarify the possible ameliorating role of garlic (Allium sativum) extract on such alterations. Material & Methods: Thirty two adult Wistar albino rats (24 females and 8 males) were used in the current study. After mating and confirmation of pregnancy, the pregnant rats were randomly allocated into four equal groups (n=6).Group1: served as control, group 2: garlic extract supplemented, group 3: CP-treated and eventually group 4: received both CP and garlic extract. At the end of the weaning period, the mothers and the offsprings of all groups were sacrificed, the kidneys were immediately excised, weighed and processed for histological and biochemical investigations. Also, blood samples were withdrawn by direct cardiac puncture and processed for estimation of the assigned biochemical parameters. Results : The renal histological sections from CP-treated mother rats displayed pronounced histopathological lesions including little and atrophied glomeruli, damaged and dilated renal tubules. However, the offsprings suffered from mild renal histopatological lesions if compared with those of their mothers. Furthermore, the levels of renal tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes were significantly decreased .On the contrary, the levels of malondialdehyde (MDA), serum urea and creatinine were significantly increased in CP-treated mother rats and their offsprings as compared with the corresponding values in the control group. On the other hand, the percentage value of caspase 3 activity was markedly elevated in the renal tissues of CP-treated mother rats and their offsprings compared to the control group. Following concomitant administration of both CP and garlic extract to the rats of group 4, the over-all histological scene of the kidney documented that there was an evident improvement so that it, more or less, resembled that of the control animals. In parallel with this, a noticeable improvement in the estimated levels of anti-oxidants, MDA, urea and creatinine as well as caspase 3activity, more or less, simulated the control levels. Conclusion: Based on the previous data, it is concluded that garlic (Allium sativum) extract has a lessening effect on the CP induced renal toxicity in pregnant rats and their offspring. Cisplatin nephrotoxicity garlic antioxidants caspase3 Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Cisplatin, carboplatin, and oxaliplatin are platinum-based chemotherapeutic drugs (Apps et al ., 2015) . These drugs persist for a long time in the blood and bind to serum proteins, especially to the serum albumin (Ferraro et al ., 2015). Generally, all these platinum drugs can induce nephrotoxicity through acute tubular necrosis of proximal tubular cells (Tixier et al ., 2016) but it is vigorously associated with CP (Landau et al., 2019) . CP is mostly used for treatment of solid cancers, like bladder cancer (Taber et al., 2020) , head and neck cancers (Lee et al., 2020) , cervical cancer (Yi et al., 2020) , testicular cancer ( de Vries et al., 2020) , ovarian (Hoskins et al ., 2000, Grabosch et al., 2019 ) and pulmonary cancers ( Nguyen et al., 2020 ) . Experimental studies on rats and mice revealed that CP leads to nephrotoxicity through formation of glutathione conjugates in blood stream (Townsend et al ., 2009) . Other studies showed that CP binds to DNA leading to arrest of DNA synthesis and replication (Wang and Lippard, 2005, Holditch et al., 2019 ) and cell apoptosis (Cullen et al ., 2007, Holditch et al., 2019 ). Moreover, Karasawa et al . (2013) stressed on that , the nephrotoxicity induced by CP is mainly attributable to toxic generation of free radicals and binding to necessary cytoplasmic molecules, especially the anti-oxidant glutathione. CP also suppresses antioxidant enzymes like superoxide dismutase (SOD) (Khynriam and Prasad, 2002 , Sun et al., 2017). Furthermore, the nephrotoxicity induced by CP is associated with elevated serum creatinine and urea, in addition, little glucose and protein may appear in urine ( Cheng et al., 2017 ) . A specific study on humans revealed that CP has a high rate of placental transfer whereas the concentration of CP in the maternal blood is approximately equal to that found in the umbilical cord blood (Marnitz et al ., 2010) . Natural products from plants and animals have been widely utilized all over the world either in the pure forms or crude extracts for protection from or treatment of various diseases (Parekh and Chanda, 2007). Allium sativum (Garlic) is one of the amost famous plants that is widely used to combat several diseases because it contains more than 33 sulfur compounds, enzymes, minerals, amino acids, vitamins especially A, B1 and C as well as fibers (Josling, 2005) . The most vitally active sulfur compound in Allium sativum is allicin and alliin which are considered as the main antioxidants and scavenging free radical compounds (Rai et al ., 2009; Nasr, 2014). Zaidi et al . (2015) declared that, allicin and alliin can improve the hepatic functions via regulation of circulating liver enzymes. Also, garlic extract has a powerful role in lowering the levels of blood cholesterol, low density lipoprotein (LDL), triglycerides ( Lau 2006; Sumioka et al., 2006 ), urea as well as blood glucose levels in diabetic mice and rabbits (Ohaeri, 2001). Garlic extract is used to lessen abdominal discomfort, diarrhea and infections of respiratory tract (Jaber and Al-Mossawi, 2007) and as an antimicrobial action (Timbo et al ., 2006). It can help to restrain some forms of cancers, heart disease, strokes and viral infections (Mansell and Reckless, 1991) , coronary diseases (Yeh et al ., 2006) , common cold (Josling, 2001) and prevention of neurotoxicity (Capraz et al ., 2006) . Previous studies confirmed that CP can penetrate the placental barrier and induce congenital malformation in fetuses ( Miyamoto et al ., 2016). On the other hand, placental transfer of garlic components was recorded by Saleh et al . (2018). Consequently, the current investigation was designed to evaluate the therapeutic role of garlic extract on the nephrotoxicity induced by CP in pregnant female rats and their offsprings. Materials And Methods 1. Chemical : CP was obtained in from of commercial Egyptian Unistin Vial from Egyptian International Medical Company. 2 . Preparation of Garlic Extract One kilogram of fresh garlic was obtained from the local market in Damanhur city, peeled and grounded by a Musermax double bladed mill and filtered through a colander until an aqueous suspension was obtained. It was diluted in double distilled water at 4 g/mL on the basis of the weight of the starting material and the resulting juice was centrifuged at 3000 Xg for 10 min to remove hard fibers. 3. Experimental Design 3.1. Experimental Animals In the current investigation, thirty-two (24 females and 8 males) Wistar albino rats weighing 180-200 g were obtained from the Hellwan Breeding Farm, Ministry of Health, Cairo, Egypt. The animals were kept in plastic cages in a well aerated room. They were handled in accordance with the guidelines of animal welfare. They were fed on standard rat chow and water ad libitum.They were housed at a controlled ambient temperature of 25±2º with 50±10% relative humidity and with a 12 h light /12 h dark cycle. After the elapse of an acclimatization period of two weeks; the animals were mated in the special mating cages (1male:3 females) overnight. After 3-4 days and ensuring of pregnancy via observation of vaginal plug and using vaginal smear method, the pregnant females rats were separated from males and were randomly categorized into four groups (n=6) as follows : Group I (control): The pregnant rats received 0.5 ml of distilled water daily through the oral route by a modified plastic syringe (intra-gastric tube) Group II (Garlic): The pregnant rats received a daily oral dose of garlic (250 mg/kg) from the 4 th day of pregnancy till the end of weaning ( Nasr and Saleh, 2014). Group III (Cisplatin): The pregnant rats received a single intraperitoneal dose of CP (5 mg/kg b.w) at the 4 th day of pregnancy, followed by 0.5 ml of distilled water daily through the oral route till the end of weaning (Naghizadeh et al ., 2008). Group IV (CP and Garlic ie. administration of CP and garlic extract): The pregnant rats received a single intraperitoneal dose of CP as in group III followed by a daily oral dose of garlic extract (250 mg/kg b.w) till the end of weaning. Ethical considerations: These experiments inclusive of animal handling and sacrifice were conducted as per the guidelines of the Bioethics Committee of DamnahurUniversity. 3.2 Sample Collection and Tissue Preparation At the end of the experiment (21 st day post-natal), the mother rats and their 21days old offsprings were weighed and sacrificed by cervical dislocation. The blood samples were immediately withdrawn by direct cardiac puncture and the serum was separated by centrifugation at 860 Xg and kept frozen at -20 o C for further biochemical analysis. The rats were dissected through a midline abdominal incision and the kidneys were immediately excised and washed in normal saline. The right kidneys were longitudinally cut into two equal halves and kept in 10 % neutral formalin for histological study. On the other side, the left kidneys were homogenized in ice cold 1.15% KCl (1 g tissue/3 mL) using a Potter-Elvenhjem type homogenizer. The homogenates were then centrifuged at 5000 rpm for 15 min at 4 ÀC and aliquots of the supernatant were used for biochemical assays. 4. Investigated Parameters 4.1. Histological Examination of Kidneys: The right kidneys from mother rats and their 21 days old offsprings were fixed in 10% neutral-buffered formalin solution for 48 hours, dehydrated in ascending grades of ethyl alcohol, cleared in xylol and embedded in paraffin blocks. Serial sections (4-5 μm) were cut using microtome (Leica RM 2125, Leica Biosystems Nussloch GmbH, Germany). The kidney sections were washed in a water bath and left in the oven for dewaxing. Thereafter, the sections were stained with hematoxylin and eosin (H&E) for examination of the general histological structure. The stained tissue-slides were mounted with Xylene and covered with cover slips. All slides were examined by a light microscope (Olympus BH-2, Olympus, Tokyo, Japan) and photographed. 4.2 Serum Analysis i. Assessment of creatinine and urea: Serum creatinine and urea were measured using standard laboratory methods and employing the commercially available diagnostic kits by an auto analyzer (BT 300, Japan) (Dickey et al ., 2005). ii. Assessment of sodium, potassium and magnesium: The serum sodium and potassium concentrations were detected by using Ireland utilizing E2A sodium/potassium reagent kit-Ireland. Serum magnesium was determined by a spectrophotometer system using kits from BioMeriecux- France. 4.3. Assessment of antioxidants and MDA in renal tissues i. Measurment of malondialdehyde and antioxidant enzymes A part of the aliquots of the supernatant of left renal tissue homogenate was used to determine the content of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and Glutathione peroxidase (GPx) enzymes. MDA was assayed by estimating the level of thiobarbituric acid reactive substances (TBARS) that was used to calcualte the extent of MDA formed as a result of membrane lipid peroxidation ( Ohkawa et al ., 1979). Antioxidant markers; SOD, CAT and GPx were measured by a colorimetric method using commercial kits (Biodiagnostic, Cairo, Egypt). SOD activity in renal tissues homogenate was detected based on the ability of the enzyme to inhibit nitroblue tetrazolium (NBT) reduction by superoxide ( Kakkar et al ., 1984). The activity of CAT enzyme was measured according to the method described by Aebi (1984). Glutathione peroxidase (GPx) was evaluated in the kidney homogenates using commercially available kits (Biodiagnostic, Egypt) based on the manufacturer’s instructions (Paglia and Valentine, 1967). ii. Flow Cytometric detection of Caspase-3 Flow cytometric detection of caspase-3 was done in order to check the number of apoptotic cells in the renal tissues for groups1, 3&4. This technique is applicable where the fluorochrome is directly binded to the primary antibody (PE and FITC conjugate). The cells were prepared appropriately. The cell suspension was adjusted to a concentration of 1 × 10 6 cell/ml with PBS/BSA buffer (phosphate buffered saline and 1% BSA). Aliquot of 100μ L of cell suspension was put into test tubes as required. The antibody (FITC rabbit anti-active caspase-3, solid as, material No.559341, catalog No. 554714, from BD Pharmingen) was added at the recommended dilution (10μ L for each sample), mixed well and incubated at room for 30 min. After that the cells were washed with 2 ml of PBS/BSA then centrifuged at 1500 rpm for 5 min and discard the resulting supernatant. The cells were re-suspended in 0.2 ml of PBS/BSA or with 0.2 ml of 0.5% Para formaldehyde in PBS/BSA if required. The data was acquired by flow cytometry. This analysis was performed in the Mansoura University Hospital using FACS (flow activated cell sorter) Calibur Flow Cytometer (Becton Dickin-son, Sunnyvale, CA, USA) equipped with a compact air-cooled low power 15 mW Argon ion laser beam (488 nm). Statistical Analysis Data were expressed as mean + standard error, (n=6 per group). Statistical analysis: one-way ANOVA followed by post hoc test. Means in the same row with different superscript (*) are significantly different (p> 0.05), *significant at p-value > 0.05, ** significant at p-value > 0.01 and ***significant at p-value > 0.001. Results 1. Body Weight Changes The results of the present work revealed that, the mean body weights of CP injected mother rats and their offsprings were significantly lowered (P<0.001) if compared with control. Following Concomitant administration of CP and garlic extract, the mean body weight was markedly elevated (P<0.001) if compared with CP group but still showing a low significant decrease for mothers and non-significant change for their offsprings if compared with the control values (Table1 and Figure1A&A1). 2. Changes in Serum Creatinine and Urea A highly significant increased levels of serum creatinine and urea (P<0.001) was recorded in CP-treated mothers and their offsprings as compared with the control group. Following administration of CP and garlic extract , the level of serum creatinine showed a highly significant decrease (P<0.001) in comparison with CP alone but still showing low significant increase for mothers and moderate significant increase for their offsprings if compared with control. On the other side, the level of serum urea, more or less, simulated the values as control for both mothers and their offsprings (Table1 and Figure 1 B-C1). 3. Changes in Serum Electrolytes The results of our study revealed that the levels of serum sodium and potassium ions were significantly decreased (P0.001) if compared with control. Following administration of CP and garlic extract, the levels of serum sodium and potassium were improved and showed non-significant change (P>0.001) in comparison with control group (Table1 and Figure D-F1). 4. Histological Findings In control and garlic treated mother rats (Figure 2A&B) and their offsprings (Figure 2A1&B1) the renal cortex appeared with normal histological structure of renal tubules and renal corpuscles. The renal corpuscle consists of glomerulus (tufts of blood capillaries) that surrounded by Bowman's space and intact Bowman's capsule. The renal tubules are represented by proximal tubules (PT), distal tubules (DT) and collecting ducts (CD). The PT is characterized by its star-shaped lumen that lined with brush bordered endothelium. The DT has relatively rounded lumen that surrounded by cubical epithelium with little microvilli. The CD has a relatively wider lumen than the PT and DT which lined with short cubical epithelium. In CP treated mother rats (Figure 2C) and their offsprings (Figure 2C1), the renal cortical sections dispalyed remarkable deleterious histological alterations but the severity of alteration was pronounced in mother rats. Such alterations included low density of renal corpuscles with relativelly wide Bowman's space, atrophied glomeruli, degenerative tubular cells and cortical tubular dilation. Following administration of CP and garlic extract, the renal cortical sections displayed remarkable amelioration in their architecture in spite of little degenerative tubules still present in some area of the renal cortical section of mothers (Figure 2D&D1). 5. Changes in Renal Tissues Antioxidants and MDA The level of SOD showed highly significant increase (P<0.001) in the renal tissues of mothers that were supplemented with garlic extract alone while that of offsprings displayed non-significant change with control. In CP-treated mothers rats and their offspring, the level of SOD showed remarkable significant decline (P<0.001) if compared with control and garlic groups. In CP-treated mother rats receiving garlic extract, the renal SOD significantly decreased if compared with CP-treated alone but still significantly lower than control; however their offspring appeared with non-signifcant changes (Table 2 & Figures 3A&A1). In garlic extract treated mother rats and their offsprings the level of renal tissues CAT appeared significantly higher than control (P<0.001). However, a highly significant decline of this enzyme was recorded in the CP-treated mothers and their offsprings. Concomitant administration of CP and garlic extract lessened such change in the CATenzyme induced by CP, notably in offsprings rather than mother which still display significant decrease than the control (Table2&Figures 3B&B1). In CP-treated mothers, the renal content of glutathione peroxidase (GPx) appeared significantly lower than control (P<0.001). Post-treatment of CP-treated mother rats with garlic extract attenuated such change in the GPx enzyme but still showing low significant decrease while their offspring appeared with significant change if compared with control (Table 2 & Figures 3C&C1). In garlic extract supplemented mother rats and their offsprings, the level of MDA in renal tissue homogenate appeared significantly lowered (P<0.001) if compared with the control. In CP-treated mothers and their offspring the level of MDA showed highly significant increase (P0.001) with control (Table 2& Figures3 D & D1). 6. Activity of Caspase-3 in Renal Tissues. The flow cytometric data , in the current research, displayed that the normal percentage value of apoptosis caused by caspase-3 in the renal tissues of control mother apparently lower than that of their offsprings (29.7% and 35.5%) respectively. However, the mean percentage value of apoptosis induced by activated caspase-3 was increased in CP-treated mother rats and their offsprings (63.6% and 48.5%) respectively if compared with control. Following administration of CP and garlic extract markedly declined the elevated percentage value of apoptosis caused by activation of caspase-3 to (31.7% and 33.6%) respectively (Figure 4). Table 1. The mean levels of body weight (g), serum creatinine (mg/dl), urea (mg/dl) and electrolytes (Na, K&Mg) of the different studied groups of mother albino rats and their offsprings. CP & Garlic n=6 CP n=6 Garlic n=6 Control n=6 Groups Parameter 194.17 ± 3.55 a(*), b (***) 178.83 ± 2.15 a (***) 202.83 ± 1.14 204.33 ± 1.99 Mothers B.wt 38.67± 1.6 30.67± 1.2 a(***) 40.83± 1.35 40.33± 1.2 21 day-offsprings 0.43 ± 0.02 a(*), b (***) 0.92 ± 0.03 a(***) 0.37 ± 0.018 0.31 ± 0.01 Mothers Creatinine (mg/dl) 0.42± 0.015 a(**), b (***) 0.64 ± 0.015 a(***) 0.39± 0.01 0.35± 0.014 21 day-offsprings 25.35 ± 1.06 33.67 ± 0.78 a(***) 22.5 ± 1.45 25.46 ± 0.67 Mothers Urea (mg/dl) 23.85± 1.35 34.4± 1.26 a(***) 23.17± 0.98 22.27± 1.4 21 day-offsprings 132.88± 0.78 99.28 ± 0.45 a(***) 134.05 ± 0.71 131.65 ± 0.71 Mothers Sodium ( mEq/L ) 134.15± 0.74 103.42 ± 0.91 a(***) 135.13 ± 1.1 137.35± 1.1 21 day-offsprings 8.53 ± 0.69 6.17 ± 0.3 a(***) 8.6 ± 0.53 9.8± 0.33 Mothers Potassium ( mEq/L ) 9.17± 0.52 7.2 ± 0.45 a(***) 9.7 ± 0.55 10.22 ± 0.57 21 day-offsprings 3.07 ± 0.27 2.8167 ± 0.64 3.12 ± 0.57 3.17 ±0.23 Mothers Magnisium ( mEq/L ) 3.35 ± 0.15 3.1 ± 0.22 3.58 ± 0.24 3.28 ±0.34 21 day-offsprings ***= highly significant **=moderately significant *=low significant a= significant with control b= significant with Cisplatin Table 2. The levels of renal tissues MDA, SOD, CAT and GPx among the different studied groups of mother's arts and their offspring. CP & Garlic n=6 CP n=6 Garlic n=6 Control n=6 Groups parameter 0.49± 0.016 b (***) 0.63± 0.015 a (***) 0.36± 0.028 a(**) 0.47± 0.02 Mothers MDA (Nmol/mg tissue protein) 0.53 ± 0.016 a (*), b (***) 0.70 ± 0.017 a(***) 0.42 ± 0.017 a (*) 0.49 ± 0.018 21 day-offsprings 8.095± 0.2 a (*), b (***) 6.11± 0.11 a(***) 10.47± 0.13 a (**) 9.13 ± 0.11 Mothers SOD (U/mg tissue protein) 18.31± 0. 14 12.15± 0. 17 a(***) 18.49± 0. 15 17.89 ± 0. 16 21 day-offsprings 0.39± 0.008 a (*), b (***) 0.218 ± 0.17 a(***) 0.42± 0.13 a (***) 0.34± 0.11 Mothers CAT (U/mg tissue protein) 0.07± 0. 013 0.024± 0.006 a(***) 0.15± 0. 009 a(***) 0.077 ± 0. 008 21 day-offsprings 3.19 ± 0.096 a (*), b (***) 1.55± 0.057 a(***) 4.08 ± 0.12 3.77± 0.11 Mothers GPx (U/mg tissue protein) 2.95± 0. 09 2.95± 0. 12 2.96 ± 0. 12 2.92 ± 0. 12 21 day-offsprings ***= highly significant **=moderately significant *=low significant a= significant with control b= significant with Cisplatin Discussion CP is a chemotherapeutic drug with widespread use in the treatment of solid tumors (Rixe , 2000; Goldwasser and Misset, 2001) . These include malignancies of breast, ovary (Hoskins et al ., 2000, Grabosch et al., 2019 ) , testis ( de Vries et al., 2020) , bladder (Taber et al., 2020) , cervical ( Yi et al., 2020) ) and lung ( Nguyen et al., 2020 ). The use of this drug has been limited due to its adverse effects on different organs. Previous studies confirmed that CP has severe deleterious side effects on pregnant mothers and their fetuses (Serkies et al ., 2011; Ghaseminezhad and Hejazi , 2015). On the other side, several researches emphasized that carrot flavor like garlic and several other flavors are transmitted from the nursing mother’s diet to her milk (Mennella and Beauchamp, 1999) . Accordingly, the current work was mainly designed to evaluate the protective effect of garlic extract against CP-iduced nephrotoxicity in pregnant mother rats and their offsprings. The obtained results of the current study revealed a remarkable significant decrease in the final body weight of CP-treated mother rats and their offsprings if compared with control. This result came in accordance with findings of previous studies (Abdelmaguid et al ., 2010; Nasr, 2013) who recordeda significant reduction in the body weight of CP-treated rats after 3–5 days post single I.P injection of 5–7.5 mg/kg of CP. The reduction of the body weight in CP-treated rats might be in part attributed to the direct toxic effect of CP on renal tubules that caused reduction in water reabsorption and excessive sodium excretion with subsequent polyuria, dehydration and reduction of body weight (Yao et al ., 2007; Azu et al ., 2010) . Another study postulated that the reduction in body weight in CP treated rats might be due to gastrointestinal toxicity with subsequent decrease in appetite, ingestion and assimilation of food (Arhoghro et al ., 2012). The reduction in body weight of offspring which their mothers received CP may be attributed to excretion of CP metabolites in milk during breast feeding. On the other side, an obvious gain in the body weight was noticed in post-treatment of CP treated -mother rats with garlic extract. Nasr and Saleh (2014 ) reported that garlic extract can maintain the body weight through regulation of renal and intestinal enzyme functions. Other studies revealed that, infants whose mothers consumed carrot during pregnancy and breastfeeding periods accepted carrot-flavored cereals more readily than infants who were exposed to this flavor for the first time ( Mennella et al ., 2001). Further study assumed that, ingestion of garlic by pregnant women leads to longer breast attachment for their infants (Mennella et al ., 1991). In contrast to obtained result concerning body weight, Dixit and Joshi (1982) was recorded a significant decrease in body weight after treatment with a garlic powder preparation by daily gavage. Such conflicting results may be attributed to the difference in exposed dose of garlic as well as the conditions of experiment. In the current work, deleterious histological changes were recorded in the renal cortex of CP-treated mother rats and their offsprings. Such changes included atrophied glomeruli, dilatation of Bowman’s space, degeneration, necrosis and detachment of the proximal tubular epithelial cell lining, dilated tubular lumina of both proximal and distal tubules. This could be due to the cytotoxic effect of CP. Similar observations were recorded in rats exposed to different doses of CP (Mansour et al ., 2006 ; Lawal and Ellis, 2011). Aydogan et al . (2008) postulated that CP has a direct toxic effect on the glomerular and tubularstructures through the generation of reactive oxygen species (ROS) that induces necrosis in renal tubular cells. The nephrotoxicity induced by CP in childhood cancer therapy has been demonstrated for some time, while new aspects of the tubular damage, including increased elimination of low molecular weight peptides and reduced excretion of some glycoprotein protein (Zimmerhackl , 1994) . Early data on CP-induced nephrotoxicity indicated that 25% of patients have an elevation in blood nitrogen levels following 1 or 2 weeks of treatment which is considered as a main cause for glomerular and tubular damage (Kovach et al ., 1974) . Pinta and Lippard (1985) suggested that, the accumulation of toxic platinum metabolites of CP inside renal tubule cells seems to be one of the most important factors implicated in induction of nephrotoxicity. Other study concluded that frequent doses of CP can directly injure the renal tubules, renal vasculature, and glomeruli through induction of oxidative stress, inflammation and apoptosis (Alhoshani et al., 2017) In the present study, a remarkable improvement was recorded in the renal tissues of mother rats administrated with garlic after treatment with CP. Several studies have demonstrated that garlic extract prevents the oxidative stress and exerts a protective effect against different toxic agents through its powerful antioxidant and free radical scavengers (Anusuya et al ., 2013; Capasso, 2013). Other studies revealed thatgarlic has a powerful cytoprotective effects to the cells of vital body organs (Assayed et al ., 2008; Hammami et al ., 2009). Serum creatinine and urea levels areconsidered the main biomarkers that efficiently determine the glomerularfiltration rate (Azu et al ., 2010). In the present study, nephrotoxicityof CP was evident from the elevated levels of serumurea and creatinine in mother rats and their offsprings. Similar observations were previously delivered in several studies (Yao et al ., 2007; Arhoghro et al ., 2012). Motegi et al . (2007) reported that, use of CP by pregnant women can exhibit a reversible elevation of serum creatinine and urea of her neonates. The elevationin the serum levels of these renal biomarkers might beattributed to the impaired renal functions (Anusuya et al ., 2013) , tubular obstruction and cytotoxicity of the renal tubules cells ( Azu et al ., 2010 ).Several studies postulated that the disturbance in renal functions by CP is mainly due to its ability to inhibit protein synthesis in thetubular cells (Adejuwon et al ., 2014) or to initiate lipid peroxidation and generatefree radicals in renal tubules (Razo-Rodríguez et al ., 2008; Saad et al ., 2009) . Aydogan et al . (2008) added that the elevation in the renal biomarkers was due to the direct cytotoxic effect of CP on the glomerular and tubular structures through the generation of ROS. In the present study, administration of CP followed by garlic extract revealed obvious recovery in the levels of serum creatinine and urea that markedly elevated by treatment of CP alone . This could be attributed to a cytoprotective effect of garlic. Our findings confirm those of other studies (Anusuya et al ., 2013; Nasr and Saleh, 2014). Razo-Rodriguez et al . (2008) assured that garlic extract can maintain the levels of serum urea and creatinine through its organo-sulfur compounds. Moreover, these compounds could enhance the antioxidant effect and inhibit lipid peroxide levels by scavenging the free radicals and increasing intracellular concentration of glutathione. The present study revealed a significant decrease in the serum sodium and potassium in CP-treated mother rats and their offspring. Such results came in agreement with the findings of previous studies (Xin et al ., 2007; Tamim et al ., 2010; Arunkumar et al ., 2012) which showed excess elimination of potassium and sodium in patients treated with CP. An early study by Daugaard et al . (1988) confirmed that; CP metabolites can inhibit the mechanism involving in electrolytes reabsorption especially in the distal segment of the nephron, resulting in hypokalemia and hyponatremia. Furthermore, CP can induce disturbance in both intestinal absorption and renal tubular reabsorption of potassium (Tamim et al ., 2010) . Another study clarified that CPcan inhibit the activity of antidiurtic hormone (ADH) leading to hypernatremia ( Surinder et al ., 2010) . Garlic was known to have various active antioxidant organo-sulfur compounds mainly S-Allylcysteine and allicin (Bongiorno et al ., 2008; Colin-Gonzalez et al ., 2012) .These compounds can enhance the cellular antioxidant enzymes, increased GPx content in the cells and scavenged the free radicals (Colin-Gonzalez et al ., 2012; Capasso, 2013) . The ameliorative effects of garlic against doxorubicin induced cardiotoxicity (Alkreathy et al ., 2010), cadmium-induced toxicity (Lawal and Ellis, 2011) and acrylamide-induced oxidative stress in various organs (Abd El-Halim and Mohamed , 2012) have been previously documented in researches. In the current study, treatment of mother rats with garlic extract alone or in combination with CP produced significant decline in MDA level and significant increase of SOD, CAT and GPx activities in the renal tissues. These findings support the antioxidant effects of garlic extract against CP-induced oxidative damage and lipid peroxidation. Lanzotti (2006) revealed that the thiosulfinates compounds of garlic play a major role in enhancing the antioxidants enzymes. Capasso (2013) added that the protective effect of garlic is mainly mediated by its highly bioavailable and significant antioxidant compounds especially S-allyl cysteine, S-allyl mercaptocyteine, allicin, and selenium that exhibited potent antioxidant activity. Moreover, the water-soluble S-allyl cysteine reduced the extent of lipid peroxidation and obviously stimulated antioxidant activities in vitro and in vivo (Almaca, 2004) . In agreement with present study, significant increase in CAT, SOD and GPx activities accompanied with significant decline in MDA was recorded in animals treated with garlic (Gorinstein et al ., 2006; Adaramoye et al ., 2008) . The obtained results in the present work concerning the reduction in the activity of renal antioxidant enzymes; CAT, SOD and GPx and elevated lipid peroxidation (MDA) in CP treated mother rats are in accordance with the findings of previous studies (Ajith et al ., 2007; Razo-Rodríguez et al ., 2008) . Sheikh-Hamad et al . (2004 ) declared that CP can liberate NO that implicated in oxidative stress and nephrotoxicity. Kart et al . (2010) added that CP is implicated in in generation of ROS that induce disturbance in membrane permeability and severe cell damage. Elevation of the MDA enhanced lipid peroxidation and increased ROS generation leading to disturbance of membrane function and integrity (Estuo, 2009). Furthermore, inhibition of antioxidant CAT, SOD, and GPx enzymes was implicated in the pathogenesis of CP-induced nephrotoxicity. Caspases are a family of proteases that play an important role in the regulation of apoptosis (Kaushal et al ., 2001). In the current investigation, caspase-3 (strong apoptotic marker) has been shown to be increased in the renal tissues of CP-treated mother's rats and their offsprings. The obtained result is in accordance with the previous studies (Kaushal et al ., 2001; Park et al ., 2002). Sheikh-Hamad et al . (2004) reported that, CP can induce apoptosis through activation of tumor necrosis factor (TNF) or messages form caspases 1, 2, 3 and 8 that activate caspase-3 in kidney. (Razzaque et al . (1999) revealed that CP increased expression of both Fas and Fas ligand in human proximal tubular epithelial cells which accelearate tha activity of caspse-3. Other researchers reported that, CP can induce apoptosis in the renal tubular epithelial cell lines resulting in activation of caspase-9, which is a good promoter for the mitochondrial apoptotic pathway (Blatt and Glick, 2001; Park et al ., 2002). Further studies explained that CP can induce apoptosis with progressive accumulation of DNA and inhibition of DNA repair pathways, through generation of reactive oxygen species (Avan et al ., 2015; Alhoshani et al., 2017). Garlic was found to attenuate the increased caspase-3 levels induced by CP treatment. Previously, it was reported that, protein s-allyl cysteine (SAC) is the most abundant compound in the garlic extract that prevents the lipid peroxidation (LPO) by ROS, the oxidative damage to DNA and apoptosis ( Mikaili et al ., 2013; Nasr and Saleh, 2014) . Conclusion In light of the demonstrated findings in this investigation, protective imprints of garlic extract against most of CP-induced histological and biochemical changes were found. Garlic extract has powerful ameliorative effects on CP-induced oxidative stress and renal damage through its antioxidant, anti-inflammatory and antiapoptotic properties through post-treatment with garlic extract. Eventually, further studies with different dose regimens and on larger number of animals over longer durations are recommended. Declarations Acknowledgments The authors would like to thank the cast of Damanhour research unit for providing facilities to bring to this work. Author contribution Conceptualization, supervision, and project administration were done by Abd El-Fattah B. M. El- Beltagy and Gamal Mohamed. Software, formal analysis, investigation, resources, data curation, software, and funding acquisition were carried out by Abd El-Fattah B. M. El- Beltagy, Mohammed A Akeel and Karoline K.Abdelaziz. Methodology and validation were investigated by Abd El-Fattah B. M. El- Beltagy, Kadry A Elbakry,and Ahmed I A Elsayed. Original draft preparation was written by Abd El-Fattah B. M. El- Beltagand Karoline K.Abdelaziz. Writing-review and editing and visualization and correspondence were done by Abd El-Fattah B. M. El- Beltagy. Funding : This work did not supported by any fund Data availability: Data are available from the authors upon request. Ethical Approval: These experiments inclusive of animal handling and sacrifice were conducted as per the guidelines of the Bioethics Committee of DamnahurUniversity. Consent to participate: Not applicable. Consent for publication: It is firmly stated that this is a genuine work and has neither been published nor is under consideration for publication elsewhere. Conflict of interest: The authors declare no competing interests. References Abd El-Halim SS, Mohamed MM (2012) Garlic powder attenuates acrylamideinduced oxidative damage in multiple organs in Rat. J Appl Sci Res.8 (1):168–173. Abdelmaguid EN, Hania NC, Noura SA (2010) Protective effect of silymarin on cisplatin-induced nephrotoxicity in rats. Pak J Nutr.9:624–636. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1295740","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[{"code":1,"date":"2022-02-03 14:54:36","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":101833759,"identity":"d6701109-b9eb-41b6-b7f0-02fc40d03d80","order_by":0,"name":"Abd El-Fattah El-Beltagy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIiWNgGAWjYBACAwbmBiiT+QADYwMepQgtjI1QdWwJJGvhMSBOizl7Y/uDH78Oy/O3n/km8XOHjRwD++GjG/Bpsew52NjY23fYcMaZ3G2SvWfSjBl40tJu4HXYjcTGBt6ew4wNB3K3SfC2HU5skOAxw6/l/sPGxr89h+3nn3/zTPIvUVpuMDY28/w4nLjhRg6bNFG2WPYkNs6WbUhP3njjmbG1bFuaMRshv5izHz7w8c0fa9t555Mf3nzbZiPHz374GF4tYMDY1gyiWCRAJBtB5WDwpw5EMn8gTvUoGAWjYBSMNAAA/5NXCz3jTFEAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-4072-4041","institution":"Damanhour University Faculty of Science","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Abd","middleName":"El-Fattah","lastName":"El-Beltagy","suffix":""},{"id":101833760,"identity":"491589ac-1358-471c-a940-f394d9e96ec5","order_by":1,"name":"Gamal Mohamed","email":"","orcid":"","institution":"Jazan University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gamal","middleName":"","lastName":"Mohamed","suffix":""},{"id":101833761,"identity":"589559dd-8aeb-4173-945c-6c232bc0d0ce","order_by":2,"name":"Mohammed A Akeel","email":"","orcid":"","institution":"Jazan University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"A","lastName":"Akeel","suffix":""},{"id":101833762,"identity":"e042b443-0ac9-48c7-ae07-4d4451f507f2","order_by":3,"name":"Karoline K. Abdelaziz","email":"","orcid":"","institution":"Damanhour University Faculty of Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Karoline","middleName":"K.","lastName":"Abdelaziz","suffix":""},{"id":101833763,"identity":"9d1d5d1e-eaa0-4f5b-ac50-800fbc98eec5","order_by":4,"name":"Kadry A Elbakry","email":"","orcid":"","institution":"Dommitta University faculty of Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kadry","middleName":"A","lastName":"Elbakry","suffix":""},{"id":101833764,"identity":"1d07c41e-7091-49b1-ac22-0d0665ec926d","order_by":5,"name":"Ahmed Ahmed I A Elsayed","email":"","orcid":"","institution":"Damanhour University Faculty of Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"Ahmed I A","lastName":"Elsayed","suffix":""}],"badges":[],"createdAt":"2022-01-25 13:29:13","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.3.rs-1295740/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-1295740/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":21066911,"identity":"ebbc72e1-ce6d-481a-921f-8f7d39b88446","added_by":"auto","created_at":"2022-05-04 15:07:53","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":152667,"visible":true,"origin":"","legend":"\u003cp\u003eA graphical histogram illustrating the body weight changes, the levels of blood creatinine and electrolytes (Na, K and Mg) among the different studied groups of mother's rats and their offspring.\u0026nbsp;Note: a highly significant decrease in the mean body weight, blood sodium\u0026amp;potassium but significant increase in the blood creatinine and urea among cisplatin induced mother's rats and their offspring. Following administration of CP and garlic extract, the levels of blood creatinine in mother rats and their offsprings\u0026nbsp;still showing significant increase (low significant and moderate significant respectively) with control while the level of urea and electrolytes are restored to the normal value as control.\u0026nbsp;\u0026nbsp;\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1295740/v2/e9a38d562198dc6f7a80fa0f.jpg"},{"id":21066913,"identity":"4de38405-3c93-4d21-9f89-d525e01c3a4e","added_by":"auto","created_at":"2022-05-04 15:07:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":358775,"visible":true,"origin":"","legend":"\u003cp\u003ePhotomicrographs of histological sections through the renal cortex among the different studied groups of mother rats and their offsprings. \u003cstrong\u003e(A\u0026amp;A1: control, B\u0026amp;B1: garlic, C\u0026amp;C1 cisplatin and D\u0026amp;D1\u003c/strong\u003e Following concomitant administration of CP and garlic extract\u003cstrong\u003e.\u003c/strong\u003e\u0026nbsp;\u0026nbsp;Note: the renal cortex appears with normal histological architecture of renal corpuscles and tubules in images A-B1, little and atrophied glomerulus (AG), damaged (arrow head) and dilated tubules (stars) in image \u003cstrong\u003eC\u0026amp;C1 \u003c/strong\u003eand obvious amelioration in the histological architecture of renal cortex in images \u003cstrong\u003eD\u0026amp;D1\u003c/strong\u003e.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAbbreviations: \u003c/strong\u003eAG; Atrophied glomeruli, BC; Bowman's capsule, BS; Bowman's space, CD; Collecting duct, DT; Distal tubules,G; Glomerulus, PT; Proximal tubules.\u003cstrong\u003e\u0026nbsp;× 400 (H\u0026amp;E).\u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u0026nbsp;\u0026nbsp;\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1295740/v2/7078993c16d03601e206f58a.jpg"},{"id":21067575,"identity":"682ddbe9-1be4-44fc-af93-2a846df61134","added_by":"auto","created_at":"2022-05-04 15:12:54","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":136111,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical histogram illustrating the levels of antioxidants (SOD, CAT and GPx) and MDA in the renal tissue among the different studied groups of mother rats and their offsprings.\u0026nbsp;Note: a highly significant in the levels of SOD, CAT and GPx (with the exception of GPx in offspring) and significant increase in the level of MDA among CP treated group. Following administration of CP and garlic extract, the levels of SOD, CAT, GPx and MDA are restored near to the control values.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1295740/v2/862e5c03f6c1ea340507b72f.jpg"},{"id":21066912,"identity":"aa53c3f0-4819-49fa-9b89-f0b21f1100b7","added_by":"auto","created_at":"2022-05-04 15:07:54","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":110085,"visible":true,"origin":"","legend":"\u003cp\u003eA flow cytometric chart showing the mean % value of caspase-3 activity in the renal tissues of mother rats and their offsprings. Note a highly % value of caspase3 activity inCP- induced mothers rats and their offspring (63.6%, 48.5%) if compared with their control (29.7%, 35.5%) respectively. Following administration of CP and garlic extract, the mean %value of caspase-3 activity in the renal cells significantly lowered (mothers rats =31.7%%, Offsprings =33.6%) if compared with CP-treated group.\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1295740/v2/6d55c3ddd3d5e052dd0bd185.jpg"},{"id":21067576,"identity":"a3f0f20d-e6d6-4ece-8d9a-40a9f9746439","added_by":"auto","created_at":"2022-05-04 15:12:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2869926,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1295740/v2/b8a5a0bd-ba2a-40c1-967c-ce5c72ca881d.pdf"}],"financialInterests":"","formattedTitle":"Modulatory Role of Garlic (Allium Sativum) Extract against Cisplatin- Induced Nephrotoxicity in Female Albino Rats and their Offspring","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCisplatin, carboplatin, and oxaliplatin are platinum-based chemotherapeutic drugs \u003cstrong\u003e(Apps \u003cem\u003eet al\u003c/em\u003e., 2015)\u003c/strong\u003e. These drugs persist for a long time in the blood and bind to serum proteins, especially to the serum albumin \u003cstrong\u003e(Ferraro \u003cem\u003eet al\u003c/em\u003e., 2015).\u0026nbsp;\u003c/strong\u003eGenerally, all these platinum drugs can induce nephrotoxicity through acute tubular necrosis of proximal tubular cells\u003cstrong\u003e\u0026nbsp;(Tixier \u003cem\u003eet al\u003c/em\u003e., 2016)\u003c/strong\u003e but it is vigorously associated with CP \u003cstrong\u003e(Landau et al., 2019)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eCP is mostly used for treatment of solid cancers, like bladder cancer \u003cstrong\u003e(Taber et al., 2020)\u003c/strong\u003e, head and neck cancers \u003cstrong\u003e(Lee et al., 2020)\u003c/strong\u003e, cervical cancer \u003cstrong\u003e(Yi et al., 2020)\u003c/strong\u003e, testicular cancer \u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ede Vries\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;et al., 2020)\u003c/strong\u003e, ovarian \u003cstrong\u003e(Hoskins \u003cem\u003eet al\u003c/em\u003e., 2000,\u003c/strong\u003e \u003cstrong\u003eGrabosch et al., 2019\u003c/strong\u003e\u003cstrong\u003e)\u0026nbsp;\u003c/strong\u003eand\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003epulmonary cancers \u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eNguyen et al., 2020\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e. Experimental studies on rats and mice revealed that CP leads to nephrotoxicity through formation of glutathione conjugates in blood stream \u003cstrong\u003e(Townsend\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e., 2009)\u003c/strong\u003e. Other studies showed that CP binds to DNA leading to arrest of DNA synthesis and replication \u003cstrong\u003e(Wang and Lippard, 2005,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eHolditch et al., 2019\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e and cell apoptosis \u003cstrong\u003e(Cullen \u003cem\u003eet al\u003c/em\u003e., 2007,\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Holditch et al., 2019\u003c/strong\u003e\u003cstrong\u003e).\u003c/strong\u003e Moreover, \u003cstrong\u003eKarasawa \u003cem\u003eet al\u003c/em\u003e. (2013)\u0026nbsp;\u003c/strong\u003estressed on that\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003ethe nephrotoxicity induced by CP is mainly attributable to toxic generation of free radicals and binding to necessary cytoplasmic molecules, especially the anti-oxidant glutathione. CP also suppresses antioxidant enzymes like superoxide dismutase (SOD) \u003cstrong\u003e(Khynriam and Prasad, 2002\u003c/strong\u003e\u003cstrong\u003e, Sun\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;et al., 2017).\u003c/strong\u003e Furthermore, the nephrotoxicity induced by CP is associated with elevated serum creatinine and urea, in addition, little glucose and protein may appear in urine \u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eCheng et al., 2017\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e. A specific study on humans revealed that CP has a high rate of placental transfer whereas the concentration of CP in the maternal blood is approximately equal to that found in the umbilical cord blood \u003cstrong\u003e(Marnitz \u003cem\u003eet al\u003c/em\u003e., 2010)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp class=\"MsoListParagraphCxSpFirst\"\u003eNatural products from plants and animals have been widely utilized all over the world either in the pure forms or crude extracts for protection from or treatment of various diseases \u003cstrong\u003e(Parekh and Chanda, 2007).\u003c/strong\u003e \u003cem\u003eAllium sativum\u003c/em\u003e (Garlic) is one of the amost famous plants that is widely used to combat several diseases because it contains more than 33 sulfur compounds, enzymes, minerals, amino acids, vitamins especially A, B1 and C as well as fibers \u003cstrong\u003e(Josling, 2005)\u003c/strong\u003e. The most vitally active sulfur compound in \u003cem\u003eAllium sativum\u003c/em\u003e is allicin and alliin which are considered as the main antioxidants and scavenging free radical compounds \u003cstrong\u003e(Rai \u003cem\u003eet al\u003c/em\u003e., 2009; Nasr, 2014). Zaidi \u003cem\u003eet al\u003c/em\u003e. (2015)\u003c/strong\u003e declared that, allicin and alliin can improve the hepatic functions via regulation of circulating liver enzymes. Also, garlic extract has a powerful role in lowering the levels of blood cholesterol, low density lipoprotein (LDL), triglycerides (\u003cstrong\u003eLau\u003c/strong\u003e \u003cstrong\u003e2006; Sumioka et al., 2006\u003c/strong\u003e), urea as well as blood glucose levels in diabetic mice and rabbits \u003cstrong\u003e(Ohaeri, 2001).\u003c/strong\u003e\u003c/p\u003e\n\u003cp class=\"MsoListParagraphCxSpLast\"\u003eGarlic extract is used to lessen abdominal discomfort, diarrhea and infections of respiratory tract \u003cstrong\u003e(Jaber and Al-Mossawi, 2007)\u0026nbsp;\u003c/strong\u003eand as an antimicrobial action \u003cstrong\u003e(Timbo \u003cem\u003eet al\u003c/em\u003e., 2006).\u0026nbsp;\u003c/strong\u003eIt can help to restrain some forms of cancers, heart disease, strokes and viral infections\u003cstrong\u003e\u0026nbsp;(Mansell and Reckless, 1991)\u003c/strong\u003e, coronary diseases \u003cstrong\u003e(Yeh \u003cem\u003eet al\u003c/em\u003e., 2006)\u003c/strong\u003e, common cold \u003cstrong\u003e(Josling, 2001)\u0026nbsp;\u003c/strong\u003eand prevention of neurotoxicity \u003cstrong\u003e(Capraz \u003cem\u003eet al\u003c/em\u003e., 2006)\u003c/strong\u003e . Previous studies confirmed that CP can penetrate the placental barrier and induce congenital malformation in fetuses (\u003cstrong\u003eMiyamoto \u003cem\u003eet al\u003c/em\u003e., 2016).\u003c/strong\u003e On the other hand, placental transfer of garlic components was recorded by \u003cstrong\u003eSaleh \u003cem\u003eet al\u003c/em\u003e. (2018).\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsequently, the current investigation was designed to evaluate the therapeutic role of garlic extract on the nephrotoxicity induced by CP in pregnant female rats and their offsprings.\u0026nbsp;\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003e1. Chemical\u003c/strong\u003e:\u0026nbsp;CP was obtained in from of commercial Egyptian Unistin Vial from Egyptian International Medical Company.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e. \u003cstrong\u003ePreparation of Garlic Extract\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne kilogram of fresh garlic was obtained from the local market in Damanhur city, peeled and grounded by a Musermax double bladed mill and filtered through a colander until an aqueous suspension was obtained. It was diluted in double distilled water at 4 g/mL on the basis of the weight of the starting material and the resulting juice was centrifuged at 3000 Xg for 10 min to remove hard fibers.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3. Experimental Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1. Experimental Animals \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the current investigation, thirty-two (24 females and 8 males) Wistar albino rats weighing 180-200 g \u0026nbsp;were obtained from the Hellwan Breeding Farm, Ministry of Health, Cairo, Egypt. The animals were kept in plastic cages in a well aerated room. They were handled in accordance with the guidelines of animal welfare. They were fed on standard rat chow and water ad libitum.They \u0026nbsp; \u0026nbsp; were housed at a controlled ambient temperature of 25\u0026plusmn;2\u0026ordm; with 50\u0026plusmn;10% relative humidity and with a 12 h light /12 h dark cycle. After the elapse of an acclimatization period of two weeks; the animals were mated in the special mating cages (1male:3 females) overnight. After 3-4 days and ensuring of pregnancy via observation of vaginal plug and using vaginal smear method, the pregnant females rats were separated from males and were randomly categorized \u0026nbsp;into four groups (n=6) as follows : \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup I\u003c/strong\u003e (control): The pregnant rats received 0.5 ml of distilled water daily through the oral route by a modified plastic syringe (intra-gastric tube)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup II\u0026nbsp;\u003c/strong\u003e(Garlic): The pregnant rats received a daily oral dose of garlic (250 mg/kg) from the 4\u003csup\u003eth\u003c/sup\u003e day of pregnancy till the end of weaning (\u003cstrong\u003eNasr and Saleh, 2014).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup III\u003c/strong\u003e (Cisplatin): The pregnant rats received a single intraperitoneal dose of CP (5 mg/kg b.w) at the 4\u003csup\u003eth\u003c/sup\u003e day of pregnancy, followed by 0.5 ml of distilled water daily through the oral route till the end of weaning \u003cstrong\u003e(Naghizadeh \u003cem\u003eet al\u003c/em\u003e., 2008). \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup IV\u003c/strong\u003e (CP and Garlic ie. administration of CP and garlic extract): \u0026nbsp; The pregnant rats received a single intraperitoneal dose of CP as in group III followed by a daily oral dose of garlic extract (250 mg/kg b.w) till the end of weaning.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical considerations:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThese experiments inclusive of animal handling and sacrifice were conducted as per the guidelines of the Bioethics Committee of DamnahurUniversity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Sample Collection and Tissue Preparation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt the end of the experiment (21\u003csup\u003est\u003c/sup\u003e day post-natal), the mother rats and their 21days old offsprings were weighed and sacrificed by cervical dislocation. \u0026nbsp; The blood samples were immediately withdrawn by direct cardiac puncture and the serum was separated by centrifugation at 860 Xg and kept frozen at -20\u003csup\u003eo\u003c/sup\u003eC for further biochemical analysis.\u0026nbsp;The rats were dissected\u0026nbsp;through a midline abdominal incision\u0026nbsp;and the kidneys were immediately excised and\u0026nbsp;washed in normal saline.\u0026nbsp;The right kidneys were longitudinally cut into two equal halves and kept in 10 % neutral formalin for histological study. On the other side, the left kidneys were homogenized in ice cold 1.15% KCl (1 g tissue/3 mL) using a Potter-Elvenhjem type homogenizer. The homogenates were then centrifuged at 5000 rpm for 15 min at 4 \u0026Agrave;C and aliquots of the supernatant were used for biochemical assays.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4. Investigated Parameters\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.1. Histological Examination of Kidneys:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe right kidneys from mother rats and their 21 days old offsprings were fixed in 10% neutral-buffered formalin solution for 48 hours, dehydrated in ascending grades of ethyl alcohol, cleared in xylol and embedded in paraffin blocks. Serial sections (4-5 \u0026mu;m) were cut using microtome (Leica RM 2125, Leica Biosystems Nussloch GmbH, Germany). The kidney sections were washed in a water bath and left in the oven for dewaxing. Thereafter, the sections were stained with hematoxylin and eosin (H\u0026amp;E) for examination of the general histological structure. The stained tissue-slides were mounted with Xylene and covered with cover slips. All slides were examined by a light microscope (Olympus BH-2, Olympus, Tokyo, Japan) and photographed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.2 Serum Analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ei. Assessment of creatinine and urea:\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerum creatinine and urea were measured using standard laboratory methods and employing the commercially available diagnostic kits by an auto analyzer (BT 300, Japan) \u003cstrong\u003e(Dickey \u003cem\u003eet al\u003c/em\u003e., 2005).\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eii. Assessment of sodium, potassium and magnesium:\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe serum sodium and potassium concentrations were detected by using Ireland utilizing E2A sodium/potassium reagent kit-Ireland. Serum magnesium was determined by a spectrophotometer system using kits from BioMeriecux- France.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.3. Assessment of antioxidants and MDA in renal tissues\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ei. Measurment of malondialdehyde\u003c/em\u003e\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eand antioxidant enzymes\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA part of the aliquots of the supernatant of left renal tissue homogenate was used to determine the content of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and Glutathione peroxidase (GPx) enzymes. MDA was assayed by estimating the level of thiobarbituric acid reactive substances (TBARS) that was used to calcualte the extent of MDA formed as a result of membrane lipid peroxidation (\u003cstrong\u003eOhkawa \u003cem\u003eet al\u003c/em\u003e.,\u003c/strong\u003e \u003cstrong\u003e1979).\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAntioxidant markers; SOD, CAT and GPx were measured by a colorimetric method using commercial kits (Biodiagnostic, Cairo, Egypt). SOD activity in renal tissues homogenate was detected based on the ability of the enzyme to inhibit nitroblue tetrazolium (NBT) reduction by superoxide (\u003cstrong\u003eKakkar\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e., 1984).\u003c/strong\u003e The activity of CAT enzyme was measured according to the method described by \u003cstrong\u003eAebi (1984).\u003c/strong\u003e Glutathione peroxidase (GPx) was evaluated in the kidney homogenates using commercially available kits (Biodiagnostic, Egypt) based on the manufacturer\u0026rsquo;s instructions \u003cstrong\u003e(Paglia and Valentine, 1967).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eii. Flow Cytometric detection of Caspase-3\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFlow cytometric detection of caspase-3 was done in order to check the number of apoptotic cells in the renal tissues for groups1, 3\u0026amp;4. This technique is applicable where the fluorochrome is directly binded to the primary antibody (PE and FITC conjugate). The cells were prepared appropriately. The cell suspension was adjusted to a concentration of 1 \u0026times; 10\u003csup\u003e6\u003c/sup\u003e cell/ml with PBS/BSA buffer (phosphate buffered saline and 1% BSA). Aliquot of 100\u0026mu; L of cell suspension was put into test tubes as required. The antibody (FITC rabbit anti-active caspase-3, solid as, material No.559341, catalog No. 554714, from BD Pharmingen) was added at the recommended dilution (10\u0026mu; L for each sample), mixed well and incubated at room for 30 min. After that the cells were washed with 2 ml of PBS/BSA then centrifuged at 1500 rpm for 5 min and discard the resulting supernatant. The cells were re-suspended in 0.2 ml of PBS/BSA or with 0.2 ml of 0.5% Para formaldehyde in PBS/BSA if required. The data was acquired by flow cytometry. This analysis was performed in the Mansoura University Hospital using FACS (flow activated cell sorter) Calibur Flow Cytometer (Becton Dickin-son, Sunnyvale, CA, USA) equipped with a compact air-cooled low power 15 mW Argon ion laser beam (488 nm).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were expressed as mean + standard error, (n=6 per group). Statistical analysis: one-way ANOVA followed by post hoc test. Means in the same row with different superscript (*) are significantly different (p\u0026gt; 0.05), *significant at p-value \u0026gt; 0.05, ** significant at p-value \u0026gt; 0.01 and ***significant at p-value \u0026gt; 0.001. \u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e1.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eBody Weight Changes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of the present work revealed that, the mean body weights of CP injected mother rats and their offsprings were significantly lowered (P\u0026lt;0.001) if compared with control. Following Concomitant administration of CP and garlic extract, the mean body weight was markedly elevated (P\u0026lt;0.001) if compared with CP group but still showing a low significant decrease for mothers and non-significant change for their offsprings if compared with the control values \u0026nbsp;\u003cstrong\u003e(Table1 and Figure1A\u0026amp;A1).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eChanges in Serum Creatinine and Urea\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA highly significant increased levels of serum creatinine and urea (P\u0026lt;0.001) was recorded in CP-treated mothers and their offsprings as compared with the control group. Following administration of CP and garlic extract , the level of serum creatinine showed a highly significant decrease (P\u0026lt;0.001) in comparison with CP alone but still showing low significant increase for mothers and moderate significant increase for their offsprings if compared with control. On the other side, the level of serum urea, more or less, simulated the values as control for both mothers and their offsprings \u003cstrong\u003e(Table1 and Figure 1 B-C1).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eChanges in Serum Electrolytes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of our study revealed that the levels of serum sodium and potassium ions were significantly decreased\u0026nbsp;(P\u0026lt;0.001) in CP-treated mothers and their offsprings while the levels of serum magnesium exihibited non-significant variation\u0026nbsp;(P\u0026gt;0.001) if compared with control.\u0026nbsp;Following administration of\u0026nbsp;CP\u0026nbsp;and\u0026nbsp;garlic extract, the levels of serum sodium and potassium were improved and showed non-significant change\u0026nbsp;(P\u0026gt;0.001) in comparison with control group\u003cstrong\u003e\u0026nbsp;(Table1 and Figure D-F1).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eHistological Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn control and garlic treated mother rats (Figure 2A\u0026amp;B) and their offsprings \u003cstrong\u003e(Figure 2A1\u0026amp;B1)\u003c/strong\u003e the renal cortex appeared with normal histological structure of renal tubules and renal corpuscles. The renal corpuscle consists of glomerulus (tufts of blood capillaries) that surrounded by Bowman\u0026apos;s space and intact Bowman\u0026apos;s capsule. The renal tubules are represented by proximal tubules (PT), distal tubules (DT) and collecting ducts (CD). The PT is characterized by its star-shaped lumen that lined with brush bordered endothelium. \u0026nbsp;The DT has relatively rounded lumen that surrounded by cubical epithelium with little microvilli. The CD has a relatively wider lumen than the PT and DT which lined with short cubical epithelium.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;In CP treated mother rats \u003cstrong\u003e(Figure 2C)\u003c/strong\u003e and their offsprings \u003cstrong\u003e(Figure 2C1),\u003c/strong\u003e the renal cortical sections dispalyed remarkable deleterious histological alterations but the severity of alteration was pronounced in mother rats. Such alterations included low density of renal corpuscles with relativelly wide Bowman\u0026apos;s space, atrophied glomeruli, degenerative tubular cells and cortical tubular dilation. Following administration of CP and garlic extract, the renal cortical sections displayed remarkable amelioration in their architecture in spite of little degenerative tubules still present in some area of the renal cortical section of mothers \u003cstrong\u003e(Figure 2D\u0026amp;D1).\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eChanges in Renal Tissues Antioxidants and MDA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe level of SOD showed highly significant increase (P\u0026lt;0.001) in the renal tissues of mothers that were supplemented with garlic extract alone while that of offsprings displayed non-significant change with control. In CP-treated mothers rats and their offspring, the level of SOD showed remarkable significant decline (P\u0026lt;0.001) if compared with control and garlic groups. In CP-treated mother rats receiving garlic extract, the renal SOD significantly decreased if compared with CP-treated alone but still significantly lower than control; however their offspring \u0026nbsp; appeared with non-signifcant changes \u003cstrong\u003e(Table 2 \u0026amp; Figures 3A\u0026amp;A1).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn garlic extract treated mother rats and their offsprings the level of renal tissues CAT appeared significantly higher than control (P\u0026lt;0.001). However, a highly significant decline of this enzyme was recorded in the CP-treated mothers and their offsprings. Concomitant administration of CP and garlic extract lessened such change in the CATenzyme induced by CP, notably in offsprings rather than mother which still display significant decrease than the control \u003cstrong\u003e(Table2\u0026amp;Figures 3B\u0026amp;B1).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn CP-treated mothers, the renal content of glutathione peroxidase (GPx) appeared significantly lower than control (P\u0026lt;0.001). Post-treatment of CP-treated \u0026nbsp;mother rats with garlic extract \u0026nbsp;attenuated such change in the GPx enzyme but still showing low significant decrease while their offspring appeared with significant change if compared with control \u003cstrong\u003e(Table 2 \u0026amp; Figures 3C\u0026amp;C1).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn garlic extract supplemented mother rats and their offsprings, the level of MDA in renal tissue homogenate appeared significantly lowered (P\u0026lt;0.001) if compared with the control. In CP-treated mothers and their offspring the level of MDA showed highly significant increase (P\u0026lt;0.001) if compared with control. Following administration of CP and garlic extract, the level of MDA showed non-significant change (P\u0026gt;0.001) with control \u003cstrong\u003e(Table 2\u0026amp; Figures3 D \u0026amp; D1).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e6.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eActivity of Caspase-3 in Renal Tissues.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe flow cytometric data , in the current research, displayed that the normal percentage value of apoptosis caused by caspase-3 in the renal tissues of control mother apparently lower than that of their offsprings (29.7% and 35.5%) respectively. However, the mean percentage value of apoptosis induced by activated caspase-3 was increased in CP-treated mother rats and their offsprings (63.6% and 48.5%) respectively if compared with control. Following administration of CP and garlic extract markedly declined the elevated percentage value of apoptosis caused by activation of caspase-3 to (31.7% and 33.6%) respectively \u003cstrong\u003e(Figure 4).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eThe mean levels of body weight (g), serum creatinine\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(mg/dl),\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;urea\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(mg/dl) and electrolytes (Na, K\u0026amp;Mg)\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eof the different studied groups of mother albino rats and their offsprings.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" dir=\"rtl\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003eCP \u0026amp; Garlic\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003en=6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003eCP\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003en=6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003eGarlic\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003en=6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003eControl\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003en=6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"171\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Groups \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eParameter\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e194.17 \u0026plusmn; 3.55 \u0026nbsp;\u003csup\u003ea(*), b (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e178.83 \u0026plusmn; 2.15\u003csup\u003e\u0026nbsp;a (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e202.83 \u0026plusmn; 1.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e204.33 \u0026plusmn; 1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003eMothers\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"92\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eB.wt\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e38.67\u0026plusmn; 1.6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e30.67\u0026plusmn; 1.2\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e40.83\u0026plusmn; 1.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e40.33\u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003e21 day-offsprings\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e0.43 \u0026plusmn; 0.02\u003csup\u003e\u0026nbsp;a(*), b (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e0.92 \u0026plusmn; 0.03\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e0.37 \u0026nbsp;\u0026plusmn; 0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e0.31 \u0026plusmn; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003eMothers\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"92\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eCreatinine\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e(mg/dl)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e0.42\u0026plusmn; 0.015 \u003csup\u003ea(**), b (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e0.64 \u0026plusmn; 0.015\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e0.39\u0026plusmn; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e0.35\u0026plusmn; 0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003e21 day-offsprings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e25.35 \u0026plusmn; 1.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e33.67 \u0026plusmn; 0.78\u003csup\u003ea(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e22.5 \u0026plusmn; 1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e25.46 \u0026plusmn; 0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003eMothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"92\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eUrea\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e(mg/dl) \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e23.85\u0026plusmn; 1.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e34.4\u0026plusmn; 1.26\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e23.17\u0026plusmn; 0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e22.27\u0026plusmn; 1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003e21 day-offsprings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e132.88\u0026plusmn; 0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e99.28 \u0026plusmn; 0.45\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e134.05 \u0026plusmn; 0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e131.65 \u0026plusmn; 0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003eMothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"92\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eSodium\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e( mEq/L )\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e134.15\u0026plusmn; 0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e103.42 \u0026plusmn; 0.91\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e135.13 \u0026plusmn; 1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e137.35\u0026plusmn; 1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003e21 day-offsprings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e8.53 \u0026plusmn; 0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e6.17 \u0026plusmn; 0.3\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e8.6 \u0026plusmn; 0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e9.8\u0026plusmn; 0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003eMothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"92\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003ePotassium\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e( mEq/L )\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e9.17\u0026plusmn; 0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e7.2 \u0026plusmn; 0.45\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e9.7 \u0026plusmn; 0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e10.22 \u0026plusmn; 0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003e21 day-offsprings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e3.07 \u0026plusmn; \u0026nbsp;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e2.8167 \u0026plusmn; 0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e3.12 \u0026plusmn; 0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e3.17 \u0026plusmn;0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003eMothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"92\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eMagnisium\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e( mEq/L ) \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"152\"\u003e\n \u003cp dir=\"LTR\"\u003e3.35 \u0026plusmn; \u0026nbsp;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"121\"\u003e\n \u003cp dir=\"LTR\"\u003e3.1 \u0026plusmn; 0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"97\"\u003e\n \u003cp dir=\"LTR\"\u003e3.58 \u0026plusmn; 0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"110\"\u003e\n \u003cp dir=\"LTR\"\u003e3.28 \u0026nbsp;\u0026plusmn;0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"79\"\u003e\n \u003cp dir=\"LTR\"\u003e21 day-offsprings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e***= highly significant \u0026nbsp; \u0026nbsp; \u0026nbsp;**=moderately significant \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;*=low significant\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ea= significant with control \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;b= significant with Cisplatin \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. The levels of renal tissues MDA, SOD, CAT and GPx among the different studied groups of mother\u0026apos;s arts and their offspring.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" dir=\"rtl\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.319018404907975%\"\u003e\n \u003cp dir=\"LTR\"\u003eCP \u0026amp; Garlic\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003en=6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.404907975460123%\"\u003e\n \u003cp dir=\"LTR\"\u003eCP\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003en=6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.177914110429448%\"\u003e\n \u003cp dir=\"LTR\"\u003eGarlic\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003en=6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.177914110429448%\"\u003e\n \u003cp dir=\"LTR\"\u003eControl\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003en=6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.920245398773005%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Groups \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eparameter\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.319018404907975%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.49\u0026plusmn; 0.016\u003csup\u003eb (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.404907975460123%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.63\u0026plusmn; 0.015\u003csup\u003e\u0026nbsp;a (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.177914110429448%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.36\u0026plusmn; 0.028\u003csup\u003ea(**)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.177914110429448%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.47\u0026plusmn; 0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\"\u003e\n \u003cp dir=\"LTR\"\u003eMothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"13.803680981595091%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eMDA\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e(Nmol/mg tissue protein)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.73309608540925%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.53 \u0026plusmn; 0.016 \u003csup\u003ea (*),\u003c/sup\u003e \u003csup\u003eb (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.352313167259787%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.70 \u0026plusmn; 0.017\u003csup\u003ea(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.9288256227758%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.42 \u0026plusmn; 0.017\u003csup\u003ea\u003c/sup\u003e \u003csup\u003e(*)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.9288256227758%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.49 \u0026plusmn; 0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.05693950177936%\"\u003e\n \u003cp dir=\"LTR\"\u003e21 day-offsprings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.319018404907975%\"\u003e\n \u003cp dir=\"LTR\"\u003e8.095\u0026plusmn; 0.2\u003csup\u003e\u0026nbsp;a (*),\u003c/sup\u003e \u003csup\u003eb (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.404907975460123%\"\u003e\n \u003cp dir=\"LTR\"\u003e6.11\u0026plusmn; 0.11\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.177914110429448%\"\u003e\n \u003cp dir=\"LTR\"\u003e10.47\u0026plusmn; 0.13\u003csup\u003e\u0026nbsp;a (**)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.177914110429448%\"\u003e\n \u003cp dir=\"LTR\"\u003e9.13 \u0026plusmn; 0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\"\u003e\n \u003cp dir=\"LTR\"\u003eMothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"13.803680981595091%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eSOD\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e(U/mg tissue protein)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.73309608540925%\"\u003e\n \u003cp dir=\"LTR\"\u003e18.31\u0026plusmn; 0. 14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.352313167259787%\"\u003e\n \u003cp dir=\"LTR\"\u003e12.15\u0026plusmn; 0. 17\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.9288256227758%\"\u003e\n \u003cp dir=\"LTR\"\u003e18.49\u0026plusmn; 0. 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.9288256227758%\"\u003e\n \u003cp dir=\"LTR\"\u003e17.89 \u0026plusmn; 0. 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.05693950177936%\"\u003e\n \u003cp dir=\"LTR\"\u003e21 day-offsprings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.319018404907975%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.39\u0026plusmn; 0.008\u003csup\u003e\u0026nbsp;a (*),\u003c/sup\u003e \u003csup\u003eb (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.404907975460123%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.218 \u0026plusmn; 0.17\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.177914110429448%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.42\u0026plusmn; 0.13\u003csup\u003e\u0026nbsp;a (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.177914110429448%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.34\u0026plusmn; 0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\"\u003e\n \u003cp dir=\"LTR\"\u003eMothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"13.803680981595091%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eCAT\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e(U/mg tissue protein) \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.73309608540925%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.07\u0026plusmn; 0. 013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.352313167259787%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.024\u0026plusmn; 0.006\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.9288256227758%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.15\u0026plusmn; 0. 009\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.9288256227758%\"\u003e\n \u003cp dir=\"LTR\"\u003e0.077 \u0026plusmn; 0. 008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.05693950177936%\"\u003e\n \u003cp dir=\"LTR\"\u003e21 day-offsprings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.319018404907975%\"\u003e\n \u003cp dir=\"LTR\"\u003e3.19 \u0026plusmn; 0.096\u003csup\u003e\u0026nbsp;a (*),\u003c/sup\u003e \u003csup\u003eb (***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.404907975460123%\"\u003e\n \u003cp dir=\"LTR\"\u003e1.55\u0026plusmn; 0.057\u003csup\u003e\u0026nbsp;a(***)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.177914110429448%\"\u003e\n \u003cp dir=\"LTR\"\u003e4.08 \u0026plusmn; 0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.177914110429448%\"\u003e\n \u003cp dir=\"LTR\"\u003e3.77\u0026plusmn; 0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.116564417177914%\"\u003e\n \u003cp dir=\"LTR\"\u003eMothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"13.803680981595091%\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eGPx\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e(U/mg tissue protein)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.73309608540925%\"\u003e\n \u003cp dir=\"LTR\"\u003e2.95\u0026plusmn; 0. 09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.352313167259787%\"\u003e\n \u003cp dir=\"LTR\"\u003e2.95\u0026plusmn; 0. 12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.9288256227758%\"\u003e\n \u003cp dir=\"LTR\"\u003e2.96 \u0026plusmn; 0. 12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.9288256227758%\"\u003e\n \u003cp dir=\"LTR\"\u003e2.92 \u0026plusmn; 0. 12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.05693950177936%\"\u003e\n \u003cp dir=\"LTR\"\u003e21 day-offsprings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e***= highly significant \u0026nbsp; \u0026nbsp; \u0026nbsp;**=moderately significant \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;*=low significant\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ea= significant with control \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;b= significant with Cisplatin \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCP is a chemotherapeutic drug with widespread use in the treatment of solid tumors \u003cstrong\u003e(Rixe\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;2000;\u003c/strong\u003e \u003cstrong\u003eGoldwasser and Misset, 2001) .\u003c/strong\u003eThese \u003cstrong\u003einclude\u003c/strong\u003e malignancies of breast, ovary \u003cstrong\u003e(Hoskins \u003cem\u003eet al\u003c/em\u003e., 2000,\u003c/strong\u003e \u003cstrong\u003eGrabosch et al., 2019\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e, testis \u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ede Vries\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;et al., 2020)\u003c/strong\u003e, bladder \u003cstrong\u003e(Taber et al., 2020)\u003c/strong\u003e, cervical (\u003cstrong\u003eYi et al., 2020)\u003c/strong\u003e) and lung \u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eNguyen et al., 2020\u003c/strong\u003e\u003cstrong\u003e).\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe use of this drug has been limited due to its adverse effects on different organs. \u0026nbsp;Previous studies confirmed that CP has severe deleterious side effects on pregnant mothers and their fetuses \u003cstrong\u003e(Serkies \u003cem\u003eet al\u003c/em\u003e., 2011;\u003c/strong\u003e\u003cstrong\u003eGhaseminezhad and Hejazi\u003c/strong\u003e\u003cstrong\u003e, 2015).\u0026nbsp;\u003c/strong\u003eOn the other side, several researches emphasized that carrot flavor like garlic and several other flavors are transmitted from the nursing mother’s diet to her milk \u003cstrong\u003e(Mennella and Beauchamp, 1999)\u003c/strong\u003e. Accordingly, the current work was mainly designed to evaluate the protective effect of garlic extract against CP-iduced nephrotoxicity in pregnant mother rats and their offsprings.\u003c/p\u003e\n\u003cp\u003eThe obtained results of the current study revealed a remarkable significant decrease in the final body weight of CP-treated mother rats and their offsprings if compared with control. This result came in accordance with findings of previous studies \u003cstrong\u003e(Abdelmaguid \u003cem\u003eet al\u003c/em\u003e., 2010; Nasr, 2013)\u0026nbsp;\u003c/strong\u003ewho recordeda significant reduction in the body weight of CP-treated rats after 3–5 days post single I.P injection of 5–7.5 mg/kg of CP. The reduction of the body weight in CP-treated rats might be in part attributed to the direct toxic effect of CP on renal tubules that caused reduction in water reabsorption and excessive sodium excretion with subsequent polyuria, dehydration and reduction of body weight \u003cstrong\u003e(Yao \u003cem\u003eet al\u003c/em\u003e., 2007;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAzu\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e., 2010)\u003c/strong\u003e. Another study postulated that the reduction in body weight in CP treated rats might be due to gastrointestinal toxicity with subsequent decrease in appetite, ingestion and assimilation of food \u003cstrong\u003e(Arhoghro \u003cem\u003eet al\u003c/em\u003e., 2012).\u003c/strong\u003e The reduction in body weight of offspring which their mothers received CP may be attributed to excretion of CP metabolites in milk during breast feeding. On the other side, an obvious gain in the body weight was noticed in\u0026nbsp;post-treatment of CP treated -mother rats with garlic extract.\u003cstrong\u003e\u0026nbsp;Nasr and Saleh (2014\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e reported that garlic extract can maintain the body weight through regulation of renal and intestinal enzyme functions. Other studies revealed that,\u0026nbsp;infants whose mothers consumed carrot during pregnancy and breastfeeding periods accepted carrot-flavored cereals more readily than infants who were exposed to this flavor for the first time (\u003cstrong\u003eMennella\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e., 2001).\u003c/strong\u003e Further study assumed that, ingestion of garlic by pregnant women leads to longer breast attachment for their infants \u003cstrong\u003e(Mennella\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e., 1991).\u003c/strong\u003e In contrast to obtained result concerning body weight, \u003cstrong\u003eDixit and Joshi (1982)\u003c/strong\u003e was recorded a significant decrease in body weight after treatment with a garlic powder preparation by daily gavage. Such conflicting results may be attributed to the difference in exposed dose of garlic as well as the conditions of experiment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the current work, deleterious histological changes were recorded in the renal cortex of CP-treated mother rats and their offsprings. Such changes included atrophied glomeruli, dilatation of Bowman’s space, degeneration, necrosis and detachment of the proximal tubular epithelial cell lining, dilated tubular lumina of both proximal and distal tubules. This could be due to the cytotoxic effect of CP. Similar observations were recorded in rats exposed to different doses of CP \u003cstrong\u003e(Mansour\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e., 2006\u003c/strong\u003e; \u003cstrong\u003eLawal\u003c/strong\u003e \u003cstrong\u003eand Ellis, 2011). Aydogan \u003cem\u003eet al\u003c/em\u003e\u003c/strong\u003e. \u003cstrong\u003e(2008)\u003c/strong\u003e postulated that CP has a direct toxic effect on the glomerular and tubularstructures through the generation of reactive oxygen species (ROS) that induces necrosis in renal tubular cells. The nephrotoxicity induced by CP in childhood cancer therapy has been demonstrated for some time, while new aspects of the tubular damage, including increased elimination of low molecular weight peptides and reduced excretion of some glycoprotein protein \u003cstrong\u003e(Zimmerhackl\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;1994)\u003c/strong\u003e. Early data on CP-induced nephrotoxicity indicated that 25% of patients have an elevation in blood nitrogen levels following 1 or 2 weeks of treatment which is considered as a main cause for glomerular and tubular damage \u003cstrong\u003e(Kovach\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e\u003c/strong\u003e.,\u003cstrong\u003e\u0026nbsp;1974)\u003c/strong\u003e. \u003cstrong\u003ePinta and Lippard (1985)\u0026nbsp;\u003c/strong\u003esuggested that, the accumulation of toxic platinum metabolites of CP inside renal tubule cells seems to be one of the most important factors implicated in induction of nephrotoxicity. Other study concluded that frequent doses of CP can directly injure the renal tubules, renal vasculature, and glomeruli through induction of oxidative stress, inflammation and apoptosis \u003cstrong\u003e(Alhoshani et al., 2017)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the present study, a remarkable improvement was recorded in the renal tissues of mother rats administrated with garlic after treatment with CP. Several studies have demonstrated that garlic extract prevents the oxidative stress and exerts a protective effect against different toxic agents through its powerful antioxidant and free radical scavengers \u003cstrong\u003e(Anusuya \u003cem\u003eet al\u003c/em\u003e., 2013; Capasso, 2013).\u0026nbsp;\u003c/strong\u003eOther studies revealed thatgarlic has a powerful cytoprotective effects to the cells of vital body organs \u003cstrong\u003e(Assayed \u003cem\u003eet al\u003c/em\u003e., 2008; Hammami \u003cem\u003eet al\u003c/em\u003e., 2009).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerum creatinine and urea levels areconsidered the main biomarkers that efficiently determine the glomerularfiltration rate \u003cstrong\u003e(Azu \u003cem\u003eet al\u003c/em\u003e., 2010).\u003c/strong\u003e In the present study, nephrotoxicityof CP was evident from the elevated levels of serumurea and creatinine in mother rats and their offsprings. Similar observations were previously delivered in several studies \u003cstrong\u003e(Yao \u003cem\u003eet al\u003c/em\u003e., 2007; Arhoghro \u003cem\u003eet al\u003c/em\u003e., 2012).\u003c/strong\u003e\u0026nbsp; \u003cstrong\u003eMotegi \u003cem\u003eet al\u003c/em\u003e. (2007)\u003c/strong\u003e reported that, use of CP by pregnant women can exhibit a reversible elevation of serum creatinine and urea of her neonates. The elevationin the serum levels of these renal biomarkers might beattributed to the impaired renal functions \u003cstrong\u003e(Anusuya\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e., 2013)\u003c/strong\u003e, tubular obstruction and cytotoxicity of the renal tubules cells (\u003cstrong\u003eAzu \u003cem\u003eet al\u003c/em\u003e., 2010\u003c/strong\u003e).Several studies postulated that the disturbance in renal functions by CP is mainly due to its ability to inhibit protein synthesis in thetubular cells \u003cstrong\u003e(Adejuwon \u003cem\u003eet al\u003c/em\u003e., 2014)\u003c/strong\u003e or to initiate lipid peroxidation and generatefree radicals in renal tubules \u003cstrong\u003e(Razo-Rodríguez \u003cem\u003eet al\u003c/em\u003e., 2008; Saad\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e., 2009)\u003c/strong\u003e.\u003cstrong\u003e\u0026nbsp;Aydogan\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e. (2008)\u003c/strong\u003e added that the elevation in the renal biomarkers was due to the direct cytotoxic effect of CP on the glomerular and tubular structures through the generation of ROS.\u003c/p\u003e\n\u003cp\u003eIn the present study, administration of CP followed by garlic extract revealed obvious recovery in the levels of serum creatinine and urea that markedly elevated by treatment of CP alone\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eThis could be attributed to a cytoprotective effect of garlic. Our findings confirm those of other studies\u003cstrong\u003e\u0026nbsp;(Anusuya \u003cem\u003eet al\u003c/em\u003e., 2013; Nasr and Saleh, 2014). \u0026nbsp;Razo-Rodriguez\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e. (2008)\u003c/strong\u003e assured that garlic extract can maintain the levels of serum urea and creatinine through its organo-sulfur compounds. Moreover, these compounds could enhance the antioxidant effect and inhibit lipid peroxide levels by scavenging the free radicals and increasing intracellular concentration of glutathione.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe present study revealed a significant decrease in the serum sodium and potassium in CP-treated mother rats and their offspring. Such results came in agreement with the findings of previous studies \u003cstrong\u003e(Xin \u003cem\u003eet al\u003c/em\u003e., 2007; Tamim \u003cem\u003eet al\u003c/em\u003e., 2010; Arunkumar \u003cem\u003eet al\u003c/em\u003e., 2012)\u003c/strong\u003e which showed excess elimination of potassium and sodium in patients treated with CP. \u0026nbsp;An early study by \u003cstrong\u003eDaugaard\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e. (1988)\u003c/strong\u003e confirmed that; CP metabolites can inhibit the mechanism involving in electrolytes reabsorption especially in the distal segment of the nephron, resulting in hypokalemia and hyponatremia. Furthermore, CP can induce disturbance in both intestinal absorption and renal tubular reabsorption of potassium\u003cstrong\u003e\u0026nbsp;(Tamim \u003cem\u003eet al\u003c/em\u003e., 2010)\u003c/strong\u003e. Another study clarified that CPcan inhibit the activity of antidiurtic hormone (ADH) leading to hypernatremia \u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eSurinder \u003cem\u003eet al\u003c/em\u003e., 2010)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eGarlic was known to have various active antioxidant organo-sulfur compounds mainly S-Allylcysteine and allicin \u003cstrong\u003e(Bongiorno \u003cem\u003eet al\u003c/em\u003e., 2008; Colin-Gonzalez \u003cem\u003eet al\u003c/em\u003e., 2012)\u003c/strong\u003e.These compounds can enhance the cellular antioxidant enzymes, increased GPx content in the cells and scavenged the free radicals \u003cstrong\u003e(Colin-Gonzalez \u003cem\u003eet al\u003c/em\u003e., 2012; Capasso, 2013)\u003c/strong\u003e. The ameliorative effects of garlic against doxorubicin induced cardiotoxicity \u003cstrong\u003e(Alkreathy\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e., 2010),\u003c/strong\u003e cadmium-induced toxicity \u003cstrong\u003e(Lawal and Ellis, 2011)\u0026nbsp;\u003c/strong\u003eand acrylamide-induced oxidative stress in various organs \u003cstrong\u003e(Abd El-Halim and Mohamed\u003c/strong\u003e, \u003cstrong\u003e2012)\u003c/strong\u003e have been previously documented in researches. \u0026nbsp; In the current study, treatment of mother rats with garlic extract alone or in combination with CP produced significant decline in MDA level and significant increase of SOD, CAT and GPx activities in the renal tissues. These findings support the antioxidant effects of garlic extract against CP-induced oxidative damage and lipid peroxidation. \u003cstrong\u003eLanzotti (2006)\u0026nbsp;\u003c/strong\u003erevealed that the thiosulfinates compounds of garlic play a major role in enhancing the antioxidants enzymes. \u0026nbsp;\u003cstrong\u003eCapasso\u003c/strong\u003e \u003cstrong\u003e(2013)\u003c/strong\u003e added that the protective effect of garlic is mainly mediated by its highly bioavailable and significant antioxidant compounds especially S-allyl cysteine, S-allyl mercaptocyteine, allicin, and selenium that exhibited potent antioxidant activity. Moreover, the water-soluble S-allyl cysteine reduced the extent of lipid peroxidation and obviously stimulated antioxidant activities in vitro and in vivo \u003cstrong\u003e(Almaca, 2004)\u003c/strong\u003e. In agreement with present study, significant increase in CAT, SOD and GPx activities accompanied with significant decline in MDA was recorded in animals treated with garlic \u003cstrong\u003e(Gorinstein \u003cem\u003eet al\u003c/em\u003e., 2006; Adaramoye \u003cem\u003eet al\u003c/em\u003e., 2008)\u003c/strong\u003e. The obtained results in the present work concerning the reduction in the activity of renal antioxidant enzymes; CAT, SOD and GPx and elevated lipid peroxidation (MDA) in CP treated mother rats are in accordance with the findings of previous studies \u003cstrong\u003e(Ajith et\u003cem\u003e\u0026nbsp;al\u003c/em\u003e., 2007; Razo-Rodríguez \u003cem\u003eet al\u003c/em\u003e., 2008)\u003c/strong\u003e.\u0026nbsp;\u003cstrong\u003eSheikh-Hamad\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e. (2004\u003c/strong\u003e) declared that CP can liberate NO that implicated in oxidative stress and nephrotoxicity. \u003cstrong\u003eKart\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e. (2010)\u003c/strong\u003e added that CP is implicated in in generation of ROS that induce disturbance in membrane permeability and severe cell damage. Elevation of the MDA enhanced lipid peroxidation and increased ROS generation leading to disturbance of membrane function and integrity \u003cstrong\u003e(Estuo, 2009).\u0026nbsp;\u003c/strong\u003e Furthermore, inhibition of antioxidant CAT, SOD, and GPx enzymes was implicated in the pathogenesis of CP-induced nephrotoxicity.\u003c/p\u003e\n\u003cp\u003eCaspases are a family of proteases that play an important role in the regulation of apoptosis \u003cstrong\u003e(Kaushal \u003cem\u003eet al\u003c/em\u003e., 2001).\u003c/strong\u003e In the current investigation, caspase-3 (strong apoptotic marker) has been shown to be increased in the renal tissues of CP-treated mother's rats and their offsprings. The obtained result is in accordance with the previous studies \u003cstrong\u003e(Kaushal \u003cem\u003eet al\u003c/em\u003e., 2001; Park \u003cem\u003eet al\u003c/em\u003e., 2002).\u003c/strong\u003e \u003cstrong\u003eSheikh-Hamad \u003cem\u003eet al\u003c/em\u003e. (2004)\u003c/strong\u003e reported that, CP can induce apoptosis through activation of tumor necrosis factor (TNF) or messages form caspases 1, 2, 3 and 8 that activate caspase-3 in kidney. \u003cstrong\u003e(Razzaque \u003cem\u003eet al\u003c/em\u003e. (1999)\u003c/strong\u003e revealed that CP increased expression of both Fas and Fas ligand in human proximal tubular epithelial cells which accelearate tha activity of caspse-3. Other researchers reported that, CP can induce apoptosis in the renal tubular epithelial cell lines resulting in activation of caspase-9, which is a good promoter for the mitochondrial apoptotic pathway \u003cstrong\u003e(Blatt and Glick, 2001; Park \u003cem\u003eet al\u003c/em\u003e., 2002).\u0026nbsp;\u003c/strong\u003eFurther studies explained that CP can induce apoptosis with progressive accumulation of DNA and inhibition of DNA repair pathways, through generation of reactive oxygen species \u003cstrong\u003e(Avan et\u003cem\u003e\u0026nbsp;al\u003c/em\u003e., 2015; Alhoshani et al., 2017).\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGarlic was found to attenuate the increased caspase-3 levels induced by CP treatment. \u0026nbsp;Previously, it was reported that, protein s-allyl cysteine (SAC) is the most abundant compound in the garlic extract that prevents the lipid peroxidation (LPO) by ROS, the oxidative damage to DNA and apoptosis \u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eMikaili\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003eet al\u003c/em\u003e., 2013; Nasr and Saleh, 2014)\u003c/strong\u003e.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn light of the demonstrated findings in this investigation, \u0026nbsp; protective imprints of garlic extract against most of CP-induced histological and biochemical changes were found. Garlic extract has powerful ameliorative effects on CP-induced oxidative stress and renal damage through its antioxidant, anti-inflammatory and antiapoptotic properties through post-treatment with garlic extract. Eventually, further studies with different dose regimens and on larger number of animals over longer durations are recommended.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the cast of Damanhour research unit for providing facilities to bring to this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConceptualization, supervision, and project administration were done by Abd El-Fattah B. M. El- Beltagy and Gamal Mohamed. Software, formal analysis, investigation, resources, data curation, software, and funding acquisition were carried out by Abd El-Fattah B. M. El- Beltagy, Mohammed A Akeel and Karoline K.Abdelaziz. Methodology and validation were investigated by Abd El-Fattah B. M. El- Beltagy, Kadry A Elbakry,and Ahmed I A Elsayed. Original draft preparation was written by Abd El-Fattah B. M. El- Beltagand Karoline K.Abdelaziz. Writing-review and editing and visualization and correspondence were done by Abd El-Fattah B. M. El- Beltagy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This work did not supported by any fund\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability: \u0026nbsp;\u003c/strong\u003eData are available from the authors upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval:\u0026nbsp;\u003c/strong\u003eThese experiments inclusive of animal handling and sacrifice were conducted as per the guidelines of the Bioethics Committee of DamnahurUniversity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eIt is firmly stated that this is a genuine work and has neither been published nor is under consideration for publication elsewhere.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eAbd El-Halim SS, Mohamed MM (2012)\u003c/strong\u003e Garlic powder attenuates acrylamideinduced oxidative damage in multiple organs in Rat. 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J Med Food. \u0026nbsp;11(3):583\u0026ndash;586.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eRazzaque MS, Koji T, Kumatori A, Taguchi T (1999\u003c/strong\u003e)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCisplatin induced apoptosis in human proximal tubular epithelial cells is associated with the activation of the Fas/Fas ligand system. Histochem Cell Biol.111:359\u0026ndash;365\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eRixe O\u003c/strong\u003e \u003cstrong\u003e(2000)\u003c/strong\u003e Platinum salts: cytotoxic mechanisms of action, mechanisms of resistance of cancer cells, interactions with ionizing radiation, and specificity of carboplatin [in French]. Bull Cancer.87:7-15.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSaad AA, Youssef MI, El-Shennawy LK (2009)\u0026nbsp;\u003c/strong\u003eCisplatin induced damage in kidney genomic DNA and nephrotoxicity in male rats: the protective effect of grape seed proanthocyanidin extract. Food Chem Toxicol.47(7):1499\u0026ndash;1506.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSaleh HA, Abd El-Aziz GS, Mustafa HN, Saleh AHA, Mal AO, Deifalla AHS, Aburas M. (2018\u003c/strong\u003e)\u003cstrong\u003e:\u003c/strong\u003e Protective effect of garlic extract against maternal and foetal cerebellar damage induced by lead administration during pregnancy in rats. Folia Morphol. 46(9):795\u0026ndash;804.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSerkies K, Wdgrzynowicz E, Jassem J (2011)\u0026nbsp;\u003c/strong\u003ePaclitaxel and cisplatin chemotherapy for ovarian cancer during pregnancy: case report and review of the literature. Arch Gynecol Obstet.283 (Suppl 1): 97\u0026ndash;100.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSheikh-Hamad D, Cacini W, Buckley AR, Isaac J, Truong LD, Tsao CC, Kishore BK (2004)\u0026nbsp;\u003c/strong\u003eCellular and molecular studies on cisplatin-induced apoptotic cell death in rat kidney.\u0026nbsp;Arch Toxicol.78:147\u0026ndash;155\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSumioka I, Hayama M, Shimokawa Y, Shiraishi S, Tokunaga A (2006)\u003c/strong\u003e Lipid-lowering effect of monascus\u003cem\u003e\u0026nbsp;\u003c/em\u003egarlic fermented extract (MGFE) in hyperlipidaemia subjects. Hiroshima. J. Med. Sci.55(2):59-64.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSun L, Liu J, Yuan Y, Zhang X, Dong Z (2018)\u0026nbsp;\u003c/strong\u003e\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/29767555/\"\u003eProtective effect of the BET protein inhibitor JQ1 in cisplatin-induced nephrotoxicity.\u0026nbsp;\u003c/a\u003e Am J Physiol Renal Physiol.315 (3):469- 478.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSurinder A, Balamurugan N, Gunaseelan K, Shasid A, Reddy KS, Adithan C\u003c/strong\u003e \u003cstrong\u003e(2010)\u0026nbsp;\u003c/strong\u003eAdverse drug reaction profile of cisplatin-based chemotherapy regimen in a tertiary care hospital in India: An evaluative study. Indian J Pharmacol. 42(1):40-43.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTaber A, Christensen E, Lamy P, Nordentoft I, Prip F, Lindskrog SV, Birkenkamp-Demtr\u0026ouml;der K, Okholm TLH, Knudsen M, Pedersen JS, Steiniche T, Agerb\u0026aelig;k M, Jensen JB, Dyrskj\u0026oslash;t L (2020)\u003c/strong\u003e \u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/32978382/\"\u003eMolecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis.\u0026nbsp;\u003c/a\u003e Nat Commun. 11(1):4858.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTamim H, Shadi L, Bassel J, Fayez K, Mohamad NA, Ashok P (2010)\u0026nbsp;\u003c/strong\u003eCisplatin-induced renal salt wasting syndrome. South Med J.10 3(8):793-799.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eTimbo BB, Ross MP, McCarthy PV, Lin CT (2006)\u0026nbsp;\u003c/strong\u003eDietary supplements in a national survey: Prevalence of use and reports of adverse events. Am. Diet Assoc\u003cem\u003e.\u003c/em\u003e106(12):1966-1974.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTixier F, Ranchon F, Iltis A, Vantard N, Schwiertz V,Bachy E, Bouafia-Sauvy F, Sarkozy C, Tournamille JF,Gyan E, Salles G, Rioufol C (2016)\u003c/strong\u003e Hematol. Oncol.35:584\u0026ndash;590.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTownsend DM, Tew KD, He L, King JB, Hanigan MH (2009)\u003c/strong\u003e Role of glutathione \u003cem\u003eS\u003c/em\u003e-transferase Pi in cisplatin-induced nephrotoxicity.Biomed. Pharmacother.63:79\u0026ndash;85.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eWang D, Lippard SJ (2005)\u0026nbsp;\u003c/strong\u003eCellular processing of platinum anticancer drugs.Nat.Rev. Drug Discov.4:307\u0026ndash;320.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eWang Y, Tang C, Cai J, Chen G, Zhang D, Zhang Z, Dong Z (2018)\u0026nbsp;\u003c/strong\u003e\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/30385753/\"\u003eINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity to protect against kidney injury.\u0026nbsp;\u003c/a\u003e Cell Death Dis. 9(11):1113\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eXin Y, Kessarin P, Neil K, Kenneth N (2007)\u0026nbsp;\u003c/strong\u003eCisplatin nephrotoxicity: A review. Am J Med Sci.334(2):116-124.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eYao X, Panichpisal K, Kurtzman N, Nugent K (2007)\u003c/strong\u003e Cisplatin nephrotoxicity: A review. Am. J.Med. Sci.334:115\u0026ndash;124.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eYeh GY, Davis RB, Phillips RS (2006)\u003c/strong\u003e Use of Complementary Therapies in Patients with Cardiovascular Disease. Am. J. Card.98(5):673-680.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eYi SA, Kim GW, Yoo J, Han JW, Kwon SH (2020)\u0026nbsp;\u003c/strong\u003e\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/32825184/\"\u003eHP1gamma Sensitizes Cervical Cancer Cells to Cisplatin through the Suppression of UBE2L3.\u0026nbsp;\u003c/a\u003eInt J Mol Sci. 21(17):5976.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eZaidi SK, Ansari SA, Ashraf GH, Jafri MA, Tabrez S, Banu N (2015)\u0026nbsp;\u003c/strong\u003e Reno-protective effect of garlic extract against immobilization stress induced changes in rats.\u003cem\u003e\u0026nbsp;\u003c/em\u003eAsian Pac J Trop Biomed. 5(5):364-369.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eZimmerhackl LB (1994)\u0026nbsp;\u003c/strong\u003eEvaluation of nephrotoxicity with renal antigens in children: role of Tamm-Horsfall protein. Eur J Clin Pharmacol.44:539\u0026ndash;42.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"environmental-science-and-pollution-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"espr","sideBox":"Learn more about [Environmental Science and Pollution Research](https://www.springer.com/journal/11356)","snPcode":"11356","submissionUrl":"https://submission.nature.com/new-submission/11356/3","title":"Environmental Science and Pollution Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Cisplatin, nephrotoxicity, garlic, antioxidants, caspase3","lastPublishedDoi":"10.21203/rs.3.rs-1295740/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1295740/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eCisplatin (CP) is one of the most powerful chemotherapeutic drugs that widely utilized in the treatment of several malignancies .However, in the late era; its use has been limited because of its hazardous health drawbacks. Previous researches confirmed that CP has severe deleterious side effects on pregnant mothers and their fetuses .Garlic (\u003cem\u003eAllium sativum\u003c/em\u003e) extract has been claimed to exhibit potent antioxidative and free radical scavenging abilities in various disease conditions.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAim: \u003c/strong\u003eThe goal of the current investigation was to throw light on the CP-induced nephrotoxic effects in pregnant albino rats and their offspring and to clarify the possible ameliorating role of garlic \u003cem\u003e(Allium sativum)\u003c/em\u003e extract on such alterations.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMaterial \u0026amp; Methods: \u003c/strong\u003eThirty two adult Wistar albino rats (24 females and 8 males) were used in the current study. After mating and confirmation of pregnancy, the pregnant rats were randomly allocated into four equal groups (n=6).Group1: served as control, group 2: garlic extract supplemented, group 3: CP-treated and eventually group 4: received both CP and garlic extract. At the end of the weaning period, the mothers and the offsprings of all groups were sacrificed, the kidneys were immediately excised, weighed and processed for histological and biochemical investigations. Also, blood samples were withdrawn by direct cardiac puncture and processed for estimation of the assigned biochemical parameters.\u0026nbsp;\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The renal histological sections from CP-treated mother rats displayed pronounced histopathological lesions including little and atrophied glomeruli, damaged and dilated renal tubules. However, the offsprings suffered from mild renal histopatological lesions if compared with those of their mothers. Furthermore, the levels of renal tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes were significantly decreased .On the contrary, the levels of malondialdehyde (MDA), serum urea and creatinine were significantly increased in CP-treated mother rats and their offsprings as compared with the corresponding values in the control group. On the other hand, the percentage value of caspase 3 activity was markedly elevated in the renal tissues of CP-treated mother rats and their offsprings compared to the control group. Following concomitant administration of both CP and garlic extract to the rats of group 4, the over-all histological scene of the kidney documented that there was an evident improvement so that it, more or less, resembled that of the control animals. In parallel with this, a noticeable improvement in the estimated levels of anti-oxidants, MDA, urea and creatinine as well as caspase 3activity, more or less, simulated the control levels.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Based on the previous data, it is concluded that garlic \u003cem\u003e(Allium sativum)\u003c/em\u003e extract has a lessening effect on the CP induced renal toxicity in pregnant rats and their offspring.\u003c/p\u003e","manuscriptTitle":"Modulatory Role of Garlic (Allium Sativum) Extract against Cisplatin- Induced Nephrotoxicity in Female Albino Rats and their Offspring","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2022-05-04 15:07:52","doi":"10.21203/rs.3.rs-1295740/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Reject","date":"2022-04-29T05:11:39+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-04-13T16:07:17+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-04-13T15:56:21+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Environmental Science and Pollution Research","date":"2022-04-12T19:38:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-04-07T05:31:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Environmental Science and Pollution Research","date":"2022-03-14T12:16:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"environmental-science-and-pollution-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"espr","sideBox":"Learn more about [Environmental Science and Pollution Research](https://www.springer.com/journal/11356)","snPcode":"11356","submissionUrl":"https://submission.nature.com/new-submission/11356/3","title":"Environmental Science and Pollution Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"955801c9-57a4-412c-8336-1abb02e43cd4","owner":[],"postedDate":"May 4th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-05-04T15:07:52+00:00","versionOfRecord":[],"versionCreatedAt":"2022-05-04 15:07:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-1295740","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1295740","identity":"rs-1295740","version":["v2"]},"buildId":"GqpaHPwrfC8PjnIFayRh5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}