Evaluation of the dose-dependent toxicity in different classes of NSAIDs on rodents with special reference to tissue architecture

Evaluation of the dose-dependent toxicity in different classes of NSAIDs on rodents with special reference to tissue architecture | 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of the dose-dependent toxicity in different classes of NSAIDs on rodents with special reference to tissue architecture sarvar jahan, Amit Sahu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8651332/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The main objective of this study is to make an assessment of the various types of NSAIDs toxicity on rodents, depending on the amount of the drug used, and with a special focus on tissue architecture. The mice were split into groups of six: group 1 was given normal saline, and group 2,3,4,5 and 6 were given orally through the feeding needle and 1 ml syringe with a single dose of Aspirin, Diclofenac, Paracetamol, Ibuprofen, and Disprin at concentrations of 1 and 2 mg/kg BW, respectively, for 10 days daily. On the 11th day of the experiment, the mice were killed by cervical dislocation. The study found that there was a significant change in BW due to the administration of NSAIDs at all concentrations in comparison with the saline group. The liver was observed as a whole in its cell death that was reversible, with damaged hepatocytes, necrosis, and shrunken central vein. The liver margins were lost due to the death of hepatocytes and the disorientation of the cartwheel arrangement of hepatocytes. When the drugs were given, the liver showed hyperchromatic cells with intermedial dysplastic cells, sinusoidal space marginal increase, and damaged hepatocytes. The kidney showed shrunken Bowman’s capsule, medullary rays, enlarged Bowman’s capsule, damaged Bowman’s capsule, and inflamed Bowman’s capsule. The present study concludes that there is a dose-dependent detrimental effect of an intake of NSAIDs and confirmed that, by increasing the concentration of the NSAIDs the toxicity was elevated at the tissue level. Toxicology NSAIDs Aspirin Diclofenac Paracetamol Ibuprofen Disprin histopathology Figures Figure 1 Figure 2 Figure 3 INTRODUCTION The non-steroidal anti-inflammatory drugs are a group of chemically heterogeneous medications widely used to control acute and chronic pain and inflammation. They are medications with analgesic (pain killing) and antipyretic (fever reducing) effects, and in higher doses anti-inflammatory effect that reduces inflammation (swelling) [1]. Most NSAIDs are nonselective and inhibit both Cox-1 and Cox-2 [2]. More than 100 million NSAIDs are prescribed throughout the world [3]. The major effect of all NSAIDs is to decrease the synthesis of prostaglandins by reversibly inhibiting cyclo-oxygenase (COX) enzymes. The present study aims to evaluate the histopathological changes that occur in the liver and kidney when different NSAIDs are co-administered. MATERIALS AND METHODS Study conduct The study was conducted in Jawaharlal Nehru Cancer Hospital and Research Centre, Idgah Hills, Bhopal- 462001 (M.P.) India CPCSEA Registration Number-CPCSEA/a/500/2001) Experimental design Total forty-four healthy of mice (Swiss albino mice, C57BL, Agouties weight 25-30gm) Animals were divided into six groups of four animals each group. Group1 (control) was administrated orally water without drugs. Groups 2, 3, 4, 5 and 6 were administrated orally with single doses of Aspirin, Diclofenac, Paracetamol, Ibuprofen and Disprin at different concentrations of 1mg & 2mg/kg BW respectively for 10 days on 11 day experimental mice were scarified by cervical dislocation. Liver and kidney were removed from the scarified mice and preserved in 10% formalin for histopathology examination [4] Statistical Analysis Resulting data were represented as mean ± SD. Statistical data was analyzed between control vs all treated groups. p<0.05 was considered statistically significant RESULT Histopathology in liver tissue Histological examination of the liver tissue showed varied damage when compared with the control group. Treated group 2 Aspirin (1mg) and group 4 Paracetamol (2mg) revealed atrophic liver in some place dysplastic hepatic cells are observed. Section revealed damaged central vein and necrosis of hepatocytes. Whereas group 2 Aspirin (2mg) and group 5 Disprin (2mg) showed damaged hepatocytes, shrunken central vein Liver margin were lost necrosis of hepatocytes. Mice dosed 1mg/kg Diclofenace (Group 3) and Group 6 Disprin (1mg) showed few dilated and shrunken central vein with few dysplastic hepatocytes. Few places the sinusoidal spaces are widen. While dosed 2mg/kg Diclofenace (Group 3) revealed there is a disorientation of cartwheel arrangement of hepatocytes. Mice dosed 1mg/kg Paracetamol (Group 4) and group 5 Ibuprofen (1mg) showed hypo-chromatic section with diluted central vein and the sinusoidal space are very. Treated group 5 Ibuprofen (1mg) revealed hyper-chromatic with inter material dysplastic cells, sinusoidal spaces marginal increase.(Figure 1) Histopathology in renal tissue Section through the kidney of Group 1 animals showed normal kidney with medulla, normal Bowman’s capsule. The section of kidney of Group 2 Aspirin (1mg) treated mice showed medullary ray, shrunken Bowman’s capsule enlarged Bowman’s capsule. Whereas Aspirin (2mg) treated mice showed damaged Bowman’s capsule, inflamed Bowman’s capsule. Group 3 Diclofenac (2mg) treated mice showed inflamed Bowman’s capsule and medullary ray. Group 4, 5 and 6 paracetamol (1mg &2mg), Ibuprofen (1mg&2mg) and Disprin (1mg&2mg) treated mice showed shrunken Bowman’s capsule, inflamed Bowman’s capsule, enlarged Bowman’s capsule and widen sinusoidal space (Figure 2) Table 1: Effect of NSAIDs on Bowman capsule of Kidney Treated group Total No. of BC NC ABC Mean %of ABC Healthy control 145.25 126 271.25 4.8 Aspirin 1mg 101.25 71.5 29.75 15.02 2mg 101.5 86.25 15.25 29.38 Diclofenac 1mg 86.25 67.5 18.75 21.45 2mg 100.5 79 21.5 22.03 Paracetamol 1mg 91 71 20 20.55 2mg 88.5 69.25 19.25 21.79 Ibuprofen 1mg 88 62.25 25.75 29.24 2mg 88.75 63 25.75 28.48 Disprin 1mg 89 70 19 21.05 2mg 88.5 76.25 12.25 13.41 NBC- Normal Bowman ’s capsule, ABC- Abnormal Bowman’s capsule Table 2: Average count of Bowman’s capsule presenting with SD and Probability value S.No Treated group Mean±SD p Value 1 Control 4.8±2.387 - 2 Aspirin 1mg 15.02 ±3.97 ns (p>0.05) 2mg 29.38±9.18 *** (p<0.001) 3 Diclofenac 1mg 21.45±3.41 * (p<0.05) 2mg 22.035±11.67 * (p0.05) 2mg 21.79±2.68 * (p<0.05) 5 Ibuprofen 1mg 29.24±3.29 ***(p<0.001) 2mg 28.48±9.55 *** (p<0.001) 6 Disprin 1mg 21.057±7.00 * (p0.05) SD: Standard Deviation , P: Probability value, p0.05: Nom-v significant, p<0.01: moderately significant, p<0.05: significant DISCUSSION Pain killer drugs come under the category of NSAIDs. NSAIDs are among the most frequently prescribed drugs worldwide because of its easy availability. The present studies were conduct to evaluate the dose dependent toxicity of different class of NSAIDs on rodent. In the present study, it was observed that when these NSAIDs were taken on regularly basis they caused gastrointestinal toxicity, kidney damage, liver injury and chromosomal aberration. In the present study, histopathology of liver revealed that the group treated with Aspirin was having atrophic liver and in some place dysplastic hepatic cell were observed and damaged hepatocytes, shrunken central vein and necrosis of hepatocytes were observed. This study supported by [5 ]who observed damage of liver cell, structure and increase in the cytoplasm of the hepatocytes in Aspirin treated mice as compared to the control group. Found Histopathology changes in liver section in Diclofenac treated group, which included cloudy swelling and hydropic degeneration of liver cell, focal sinusoidal and vena centralis dilatation, fibrous tissues proliferation and focal necrosis [6] In the present study histopathology of liver revealed that the group treated with Diclofenac was having dilated and shrunken central vein with dysplastic hepatocytes, wider sinusoidal space and disorientation of cartwheel arrangement of hepatocytes. Histopathology of liver treated with Ibuprofen revealed hypo-chromatic cells, increased sinusoidal spaces margin increase and intermittent dysplastic cell. In the study of [7] the TS of liver tissue of the Ibuprofen group has extensive degenerative changes, centrilobular, necrosis, lymphocyte accusation and bleeding. In Paracetamol, mice treated hypo-chromatic section with dilated central vein, and atrophic liver and in some places, dysplastic hepatic cells were observed. In the study of [8] various histopathological changes of liver were observed which includes congestion of sinusoidal and centrilobular necrosis, piknotic nuclear changes and micron vesicular fatty change. In the present study the histopathology of kidney section of mice fed with Aspirin (1mg & 2mg) revealed that Medullary rays, shrunken Bowman’s capsule and enlarged Bowman’s capsule. In comparison to the control group more damaged Bowman’s capsule was found in the Aspirin treated group. In case of Diclofenac (1mg or 2mg) group showed Medullary rays and inflamed Bowman’s capsule. In the study of [9] it was found that Histopathological changes in kidney section in Diclofenac treated group included cloudy swelling and hydropic degeneration were seen in the tubular epithelial cell of kidney tissue per tubular lymphocyte infiltration, epithelial cell necrosis toxicity in Glomerulus. In the study of [10] no significant toxicity was seen in the kidney in histopathological analysis. Whereas in the present study the histopathology of kidney section of mice fed with paracetamol (1mg & 2mg) revealed that Medullary rays, shrunken Bowman’s capsule and enlarged Bowman’s capsule. CONCLUSION The advent of allopathic treatments has been a great advantage to mankind in terms of fast pain relief. Painkillers are considered the best drug among all medications for every kind of pain. NSAIDs form the backbone of analgesics and are the most recognized pain relievers like Aspirin, Disprin, Ecospirin, Brufen, Ibuprofen, Paracetamol, Diclofenac, and Morphine. The current research was an endeavor to investigate the toxic impact of NSAIDs on mammalian cells. Replace the birds' extinction with vulture population decline due to environmental toxicity. The world is losing the vulture population, which was inferred from the tainted carcasses, particularly of livestock like Cows & Buffalos that had been administered Diclofenac. The present research too focused on the same toxicity event. The renal glomerulus has exhibited a reversed toxicity pattern for Ibuprofen whereas, by the order of, Aspirin, Diclofenac and, scored more damaged glomerulus. The present investigation interprets that there is a dose-dependent negative impact of NSAIDs intake and also corroborates that the rising concentration of NSAIDs leads to the increase in toxicity at both genomic and tissue levels. The present investigation indicates the necessity of running more comprehensive trials on the toxic effects of various doses of NSAIDs to arrive at the possible safe dose level if any. The current research is also going to monitor the inappropriate use of NSAIDs in cattle and humans per se. It is not only going to save the organ system destroyed by NSAIDs but also protect the endangered species like VULTURE and other Aves as well. References Nordqvist, Christian. (2014). "What Is Stress? How to Deal with Stress." Medical News Today. MediLexicon. Zimmerman HJ. (1999), The NSAIDs. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott 517-41. Jürgen Steinmeyer (2000), Pharmacological basis for the therapy of pain and inflammation with nonsteroidal anti-inflammatory drugs, Arthritis Research 2(5):379-85. Palipoch S. A review of oxidative stress in acute kidney injury: protective role of medicinal plants-derived antioxidants. African Journal of Traditional, Complementary and Alternative Medicines. 2013 Jun 18;10(4):88-93. Abdel- Tawab H.Mossa, Tarek M. Heikal, Enayat Abdel Aziz Omara (2014). Liver damage associated with exposure to aspirin and diazinon in male rats and the ameliorative effect of selenium. Biomedicine and aging pathology. Vol 4(2): 137-145. H. Sarfaraz, K. Farah and N. Ganesh (2006). Histopathologic study of kidney tissues, by different doses of diclofenac sodium (NSAIDs) in mice models. Open Research Journal, Vol 23(3): 39417. Nordqvist, Christian. (2015). "What Is Stress? 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Histological and ultrastructural studies on the effect of diclofenac sodium on the renal cortex of fetuses of albino mice. Global Journal of Pharmacology. 2014;8(3):369-77. Manov I, Motanis H, Frumin I, Iancu TC. Hepatotoxicity of anti-inflammatory and analgesic drugs: ultrastructural aspects. Acta Pharmacologica Sinica. 2006 Mar;27(3):259-72. Wallace JL, Bak A, McKnight W, Asfaha S, Sharkey KA, MacNaughton WK. Cyclooxygenase 1 contributes to inflammatory responses in rats and mice: implications for gastrointestinal toxicity. Gastroenterology. 1998 Jul 1;115(1):101-9. Additional Declarations The authors declare no competing interests. Animal Ethics Statement: All experimental procedures involving non-human vertebrates were conducted in accordance with institutional and national guidelines for the care and use of laboratory animals. The study was carried out at Jawaharlal Nehru Cancer Hospital and Research Centre, Idgah Hills, Bhopal–462001 (M.P.), India, after obtaining approval and oversight from the Institutional Animal Ethics Committee. The facility is registered with the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India (Registration No. CPCSEA/a/500/2001). Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board 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-8651332","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":577592506,"identity":"20872b39-c550-4e9b-9b82-66a19302fc59","order_by":0,"name":"sarvar 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09:25:20","extension":"xml","order_by":38,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":47565,"visible":true,"origin":"","legend":"","description":"","filename":"rs86513320structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8651332/v1/d65d1f9c0cb8d93b22bbad73.xml"},{"id":100874256,"identity":"c44a3259-00e1-4ab3-b25b-8ccdc65dcd03","added_by":"auto","created_at":"2026-01-22 10:00:12","extension":"html","order_by":39,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":55718,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8651332/v1/9cf9309d3705b55de65162eb.html"},{"id":100874225,"identity":"b09cbb6b-e163-4bd0-8f3a-9f1937b84803","added_by":"auto","created_at":"2026-01-22 10:00:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":359738,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePhotograph of liver of the normal control group; (A) Photograph of liver \u0026nbsp;induce by 1 \u0026amp; 2 mg/kg BW of Aspirin; (B) Photograph of liver induce by 1 \u0026amp; 2 mg/kg BW of Diclofenac; (C) Photograph of liver induce by 1 \u0026amp; 2 mg/kg BW of Paracetamol; (D) Photograph of liver induce by 1 \u0026amp; 2 mg/kg BW of Ibuprofen; (E) Photograph of liver induce by 1 \u0026amp; 2 mg/kg BW of Disprin; (F)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8651332/v1/d6357cbd1ba0ecc24bc7c521.png"},{"id":100874227,"identity":"23247132-a1fd-476f-bf4c-8d8568e992ec","added_by":"auto","created_at":"2026-01-22 10:00:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":240137,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePhotograph of kidney of the normal control group; (A) Photograph of kidney induce by 1 \u0026amp; 2 mg/kg BW of Aspirin; (B) Photograph of kidney induce by 1 \u0026amp; 2 mg/kg BW of Diclofenac; (C)) Photograph of kidney induce by 1 \u0026amp; 2 mg/kg BW of Paracetamol; (D) Photograph of kidney induce by 1 \u0026amp; 2 mg/kg BW of Ibuprofen; (E) Photograph of kidney induce by 1 \u0026amp; 2 mg/kg BW of Disprin; (F)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8651332/v1/1cf793c9e7bb9bfd9d840906.png"},{"id":100950268,"identity":"06ac0ef8-0b4f-4e90-a3e8-eb843ac469fa","added_by":"auto","created_at":"2026-01-23 07:07:26","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":15140,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA:\u003c/strong\u003eNormal control, \u003cstrong\u003eB:\u003c/strong\u003e Aspirin (1mg), \u003cstrong\u003eC:\u003c/strong\u003e Aspirin (2mg), \u003cstrong\u003eD:\u003c/strong\u003eDiclofenac (1mg), \u003cstrong\u003eE:\u003c/strong\u003e Diclofenac (2mg), \u003cstrong\u003eF:\u003c/strong\u003e Paracetamol (1mg), \u003cstrong\u003eG: \u003c/strong\u003eparacetamol (2mg), \u003cstrong\u003eH:\u003c/strong\u003e Ibuprofen (1mg), \u003cstrong\u003eI:\u003c/strong\u003e Ibuprofen (2mg), \u003cstrong\u003eJ:\u003c/strong\u003eDisprin (1mg), \u003cstrong\u003eK:\u003c/strong\u003e Disprin (2mg)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8651332/v1/0daf19c6f7891de72dc03f04.png"},{"id":101942735,"identity":"2a7b985e-fb8e-4fe1-9e5f-3059e404023c","added_by":"auto","created_at":"2026-02-05 09:36:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1393200,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8651332/v1/a0e3133c-0f80-4585-83e2-1d9881d7443b.pdf"}],"financialInterests":"\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnimal Ethics Statement:\u003c/strong\u003e\u003cbr\u003e\nAll experimental procedures involving non-human vertebrates were conducted in accordance with institutional and national guidelines for the care and use of laboratory animals. The study was carried out at Jawaharlal Nehru Cancer Hospital and Research Centre, Idgah Hills, Bhopal–462001 (M.P.), India, after obtaining approval and oversight from the Institutional Animal Ethics Committee. The facility is registered with the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India (Registration No. CPCSEA/a/500/2001).\u003c/p\u003e","formattedTitle":"\u003cp\u003e\u003cstrong\u003eEvaluation of the dose-dependent toxicity in different classes of NSAIDs on rodents with special reference to tissue architecture\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe non-steroidal anti-inflammatory drugs are a group of chemically heterogeneous medications widely used to control acute and chronic pain and inflammation. They are medications with analgesic (pain killing) and antipyretic (fever reducing) effects, and in higher doses anti-inflammatory effect that reduces inflammation (swelling) [1]. Most NSAIDs are nonselective and inhibit both Cox-1 and Cox-2 [2]. More than 100\u0026nbsp;million NSAIDs are prescribed throughout the world [3]. The major effect of all NSAIDs is to decrease the synthesis of prostaglandins by reversibly inhibiting cyclo-oxygenase (COX) enzymes.\u003c/p\u003e \u003cp\u003eThe present study aims to evaluate the histopathological changes that occur in the liver and kidney when different NSAIDs are co-administered.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e\u003cstrong\u003eStudy conduct\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in Jawaharlal Nehru Cancer Hospital and Research Centre, Idgah Hills, Bhopal- 462001 (M.P.) India CPCSEA Registration Number-CPCSEA/a/500/2001)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExperimental design\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTotal forty-four healthy of mice (Swiss albino mice, C57BL, Agouties weight 25-30gm) Animals were divided into six groups of four animals each group. Group1 (control) was administrated orally water without drugs. Groups 2, 3, 4, 5 and 6 were administrated orally with single doses of Aspirin, Diclofenac, Paracetamol, Ibuprofen and Disprin at different concentrations of 1mg \u0026amp; 2mg/kg BW respectively for 10 days on 11 day experimental mice were scarified by cervical dislocation. Liver and kidney were removed from the scarified mice and preserved in 10% formalin for histopathology examination\u0026nbsp;[4]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResulting data were represented as mean \u0026plusmn; SD. Statistical data was analyzed between control vs all treated groups. p\u0026lt;0.05 was considered statistically significant\u003c/p\u003e"},{"header":"RESULT","content":"\u003cp\u003e\u003cstrong\u003eHistopathology in liver tissue\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHistological examination of the liver tissue showed varied damage when compared with the control group. Treated group 2 Aspirin (1mg) and group 4 Paracetamol (2mg) revealed atrophic liver in some place dysplastic hepatic cells are observed. Section revealed damaged central vein and necrosis of hepatocytes. Whereas group 2 Aspirin (2mg) and group 5 Disprin (2mg) showed damaged hepatocytes, shrunken central vein Liver margin were lost necrosis of hepatocytes. Mice dosed 1mg/kg Diclofenace (Group 3) and Group 6 Disprin (1mg) showed few dilated and shrunken central vein with few dysplastic hepatocytes. Few places the sinusoidal spaces are widen. While dosed 2mg/kg Diclofenace (Group 3) revealed there is a disorientation of cartwheel arrangement of hepatocytes. Mice dosed 1mg/kg Paracetamol (Group 4) and group 5 Ibuprofen (1mg) showed hypo-chromatic section with diluted central vein and the sinusoidal space are very. Treated group 5 Ibuprofen (1mg) revealed hyper-chromatic with inter material dysplastic cells, sinusoidal spaces marginal increase.(Figure 1)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistopathology in renal tissue\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSection through the kidney of Group 1 animals showed normal kidney with medulla, normal Bowman\u0026rsquo;s capsule. The section of kidney of Group 2 Aspirin (1mg) treated mice showed medullary ray, shrunken Bowman\u0026rsquo;s capsule enlarged Bowman\u0026rsquo;s capsule. Whereas Aspirin (2mg) treated mice showed damaged Bowman\u0026rsquo;s capsule, inflamed Bowman\u0026rsquo;s capsule. Group 3 Diclofenac (2mg) treated mice showed inflamed Bowman\u0026rsquo;s capsule and medullary ray. Group 4, 5 and 6 paracetamol (1mg \u0026amp;2mg), Ibuprofen (1mg\u0026amp;2mg) and Disprin (1mg\u0026amp;2mg) treated mice showed shrunken Bowman\u0026rsquo;s capsule, inflamed Bowman\u0026rsquo;s capsule, enlarged Bowman\u0026rsquo;s capsule and widen sinusoidal space (Figure 2)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Effect of NSAIDs on Bowman capsule of Kidney\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"565\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTreated group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal No.\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eof BC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eABC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean %of\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eABC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHealthy control\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e145.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e271.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAspirin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e101.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e71.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e29.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e15.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e101.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e86.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e15.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e29.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDiclofenac\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e86.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e67.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e18.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e21.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e100.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e21.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e22.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eParacetamol\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e20.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e88.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e69.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e19.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e21.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIbuprofen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e62.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e25.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e29.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e88.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e25.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e28.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDisprin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e21.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e88.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e76.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e12.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e13.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNBC-\u003c/strong\u003eNormal Bowman\u003cstrong\u003e\u0026rsquo;s\u0026nbsp;\u003c/strong\u003ecapsule,\u003cstrong\u003eABC-\u003c/strong\u003eAbnormal Bowman\u0026rsquo;s capsule\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: \u0026nbsp;Average count of Bowman\u0026rsquo;s capsule presenting with SD and Probability value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eS.No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 228px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Treated \u0026nbsp;group\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Mean\u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;p Value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 228px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.8\u0026plusmn;2.387\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAspirin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15.02 \u0026plusmn;3.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ens (p\u0026gt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29.38\u0026plusmn;9.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e*** (p\u0026lt;0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDiclofenac\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21.45\u0026plusmn;3.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e* (p\u0026lt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22.035\u0026plusmn;11.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e* (p\u0026lt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eParacetamol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20.55\u0026plusmn;6.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ens (p\u0026gt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21.79\u0026plusmn;2.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e* (p\u0026lt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eIbuprofen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29.24\u0026plusmn;3.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e***(p\u0026lt;0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28.48\u0026plusmn;9.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e*** (p\u0026lt;0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDisprin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21.057\u0026plusmn;7.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e* (p\u0026lt;0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2mg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e13.41\u0026plusmn;2.70\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ens (p\u0026gt;0.05)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eSD:\u0026nbsp;\u003c/strong\u003eStandard Deviation\u003cstrong\u003e, P:\u0026nbsp;\u003c/strong\u003eProbability value, \u003cstrong\u003ep\u0026lt;0.001:\u003c/strong\u003e highly significant, \u003cstrong\u003ep\u0026gt;0.05:\u003c/strong\u003e Nom-v significant, \u003cstrong\u003ep\u0026lt;0.01:\u003c/strong\u003e moderately significant, \u003cstrong\u003ep\u0026lt;0.05:\u003c/strong\u003e significant \u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003ePain killer drugs come under the category of NSAIDs. NSAIDs are among the most frequently prescribed drugs worldwide because of its easy availability. The present studies were conduct to evaluate the dose dependent toxicity of different class of NSAIDs on rodent. In the present study, it was observed that when these NSAIDs were taken on regularly basis they caused gastrointestinal toxicity, kidney damage, liver injury and chromosomal aberration.\u003c/p\u003e\n\u003cp\u003eIn the present study, histopathology of liver revealed that the group treated with Aspirin was having atrophic liver and in some place dysplastic hepatic cell were observed and damaged hepatocytes, shrunken central vein and necrosis of hepatocytes were observed. This study supported by [5 ]who observed damage of liver cell, structure and increase in the cytoplasm of the hepatocytes in Aspirin treated mice as compared to the control group. Found Histopathology changes in liver section in Diclofenac treated group, which included cloudy swelling and hydropic degeneration of liver cell, focal sinusoidal and vena centralis dilatation, fibrous tissues proliferation and focal necrosis [6]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the present study histopathology of liver revealed that the group treated with Diclofenac was having dilated and shrunken central vein with dysplastic hepatocytes, wider sinusoidal space and disorientation of cartwheel arrangement of hepatocytes. Histopathology of liver treated with Ibuprofen revealed hypo-chromatic cells, increased sinusoidal spaces margin increase and intermittent dysplastic cell. In the study of [7] the TS of liver tissue of the Ibuprofen group has extensive degenerative changes, centrilobular, necrosis, lymphocyte accusation and bleeding. In Paracetamol, mice treated hypo-chromatic section with dilated central vein, and atrophic liver and in some places, dysplastic hepatic cells were observed. In the study of [8] various histopathological changes of liver were observed which includes congestion of sinusoidal and centrilobular necrosis, piknotic nuclear changes and micron vesicular fatty change. In the present study the histopathology of kidney section of mice fed with Aspirin (1mg \u0026amp; 2mg) revealed that Medullary rays, shrunken Bowman\u0026rsquo;s capsule and enlarged Bowman\u0026rsquo;s capsule. In comparison to the control group more damaged Bowman\u0026rsquo;s capsule was found in the Aspirin treated group. \u0026nbsp;In case of Diclofenac (1mg or 2mg) group showed Medullary rays and inflamed Bowman\u0026rsquo;s capsule. In the study of [9] it was found that Histopathological changes in kidney section in Diclofenac treated group included cloudy swelling and hydropic degeneration were seen in the tubular epithelial cell of kidney tissue per tubular lymphocyte infiltration, epithelial cell necrosis toxicity in Glomerulus.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the study of [10] no significant toxicity was seen in the kidney in histopathological analysis. Whereas in the present study the histopathology of kidney section of mice fed with paracetamol (1mg \u0026amp; 2mg) revealed that Medullary rays, shrunken Bowman\u0026rsquo;s capsule and enlarged Bowman\u0026rsquo;s capsule.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe advent of allopathic treatments has been a great advantage to mankind in terms of fast pain relief. Painkillers are considered the best drug among all medications for every kind of pain. NSAIDs form the backbone of analgesics and are the most recognized pain relievers like Aspirin, Disprin, Ecospirin, Brufen, Ibuprofen, Paracetamol, Diclofenac, and Morphine. The current research was an endeavor to investigate the toxic impact of NSAIDs on mammalian cells. Replace the birds\u0026apos; extinction with vulture population decline due to environmental toxicity. The world is losing the vulture population, which was inferred from the tainted carcasses, particularly of livestock like Cows \u0026amp; Buffalos that had been administered Diclofenac. The present research too focused on the same toxicity event. The renal glomerulus has exhibited a reversed toxicity pattern for Ibuprofen whereas, by the order of, Aspirin, Diclofenac and, scored more damaged glomerulus. The present investigation interprets that there is a dose-dependent negative impact of NSAIDs intake and also corroborates that the rising concentration of NSAIDs leads to the increase in toxicity at both genomic and tissue levels. The present investigation indicates the necessity of running more comprehensive trials on the toxic effects of various doses of NSAIDs to arrive at the possible safe dose level if any. The current research is also going to monitor the inappropriate use of NSAIDs in cattle and humans per se. It is not only going to save the organ system destroyed by NSAIDs but also protect the endangered species like VULTURE and other Aves as well.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eNordqvist, Christian. (2014). \u0026quot;What Is Stress? How to Deal with Stress.\u0026quot; Medical News Today. MediLexicon.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eZimmerman HJ. (1999), The NSAIDs. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott 517-41. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eJ\u0026uuml;rgen Steinmeyer (2000), Pharmacological basis for the therapy of pain and inflammation with nonsteroidal anti-inflammatory drugs, Arthritis Research 2(5):379-85.\u003c/li\u003e\n \u003cli\u003ePalipoch S. A review of oxidative stress in acute kidney injury: protective role of medicinal plants-derived antioxidants. African Journal of Traditional, Complementary and Alternative Medicines. 2013 Jun 18;10(4):88-93.\u003c/li\u003e\n \u003cli\u003eAbdel- Tawab H.Mossa, Tarek M. Heikal, Enayat Abdel Aziz Omara (2014). Liver damage associated with exposure to aspirin and diazinon in male rats and the ameliorative effect of selenium. Biomedicine and aging pathology. Vol 4(2): 137-145.\u003c/li\u003e\n \u003cli\u003eH. Sarfaraz, K. Farah and N. Ganesh (2006). Histopathologic study of kidney tissues, by different doses of diclofenac sodium (NSAIDs) in mice models. Open Research Journal, Vol 23(3): 39417.\u003c/li\u003e\n \u003cli\u003eNordqvist, Christian. (2015). \u0026quot;What Is Stress? How to Deal with Stress.\u0026quot; Medical News Today. MediLexicon.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eInthisham, Thanikachalam, John Paul, MS, Ignacio (2010), Histopathological study of the hepatic and renal toxicity associated with the co-administration of Imatinib and Acetaminophen in a preclinical mouse model. Malaysian J Pathol.Vol 32(1):11.\u003c/li\u003e\n \u003cli\u003eG. Aydin, A. GokcMen, M. Oncu E. Ccek, N. Karahan, O. Gokalp (2003). Histopathologic Changes in Liver and Renal Tissues Induced by Different Doses of Diclofenac Sodium in Rats. Turk J Vet Anim Sci. Vol 27:1131-1140.\u003c/li\u003e\n \u003cli\u003eWalter H. H. (2010). Nonsteroidal Anti-Inflammatory Drugs and the Kidney. Pharmaceuticals (Basel). Vol 3(7): 2291\u0026ndash;2321.\u003c/li\u003e\n \u003cli\u003eJohn L. Wallace, Adrian Bak, Webb Mcknight, Samuel Asfaha, Kelth A. Sharkey, and Wallace K. MacnauGhton (1998), Cyclooxygenase 1 Contributes to Inflammatory Responses in Rats and Mice: Implications for Gastrointestinal Toxicity Gastroenterology.Vol 115: 101\u0026ndash;109.\u003c/li\u003e\n \u003cli\u003ePayasi, Anurag, Gupta Ankush, Chaudhary Manu, Dwivedi K. Vivek, Singh Brij Mohan and Shrivastava M. Sanjay (2010). \u0026nbsp;Sub-Acute Toxicity Studies of Paracetamol Infusion in \u0026nbsp; Mus Musculus Mice. Int.J.Drug Dev. \u0026amp; Res.Vol 2(1):157-163.\u003c/li\u003e\n \u003cli\u003eSarawoot, Chuchard and Prasit (2013), Histopathology of Small Intestine Induced by Cisplatin in Male WistarRats. Walailak J. Sci. \u0026amp;Tech.Vol10 (6): 657-663.\u003c/li\u003e\n \u003cli\u003eZimmerman HJ. (1999), The NSAIDs. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott.517-41.\u003c/li\u003e\n \u003cli\u003eH. Sarfaraz, K. Farah and N. Ganesh (2006).\u0026nbsp;Histopathologic study of kidney tissues, by different doses of diclofenac sodium (NSAIDs) in mice models. Open Research Journal, Vol 23(3): 39417.\u003c/li\u003e\n \u003cli\u003ePalipoch S, Punsawad C, Chinnapun D, Suwannalert P. Amelioration of cisplatin-induced nephrotoxicity in rats by curcumin and \u0026alpha;-tocopherol. Tropical Journal of Pharmaceutical Research. 2013;12(6):973-9.\u003c/li\u003e\n \u003cli\u003eCook JC, Jacobson CF, Gao F, Tassinari MS, Hurtt ME, DeSesso JM. Analysis of the nonsteroidal anti‐inflammatory drug literature for potential developmental toxicity in rats and rabbits. Birth Defects Research Part B: Developmental and Reproductive Toxicology. 2003 Feb;68(1):5-26.\u003c/li\u003e\n \u003cli\u003eAdel Elnashar A, Kamal HI, Magdy MA, Gamal T, Hamid L, Ragab SF, Khodier SA, Mohamed A, Kamel MM, El-shahawy AA, Yehia DA. Review on diclofenac toxicities in different organs. Ain Shams Journal of Forensic Medicine and Clinical Toxicology. 2024 Jan 1;42(1):10-24.\u003c/li\u003e\n \u003cli\u003eAziz ND, Ouda MH, Ubaid MM. Comparing the toxic effects of nonsteroidal anti-inflammatory drugs (celecoxib and ibuprofen) on heart, liver, and kidney in rats. Asian J Pharm Clin Res. 2018;11(6):482-5.\u003c/li\u003e\n \u003cli\u003eBoelsterli UA, Zimmerman HJ, Kretz-Rommel A. Idiosyncratic liver toxicity of nonsteroidal antiinflammatory drugs: molecular mechanisms and pathology. Critical reviews in toxicology. 1995 Jan 1;25(3):207-35.\u003c/li\u003e\n \u003cli\u003eSabry SA, Sakr SM, Shahin MA. Histological and ultrastructural studies on the effect of diclofenac sodium on the renal cortex of fetuses of albino mice. Global Journal of Pharmacology. 2014;8(3):369-77.\u003c/li\u003e\n \u003cli\u003eManov I, Motanis H, Frumin I, Iancu TC. Hepatotoxicity of anti-inflammatory and analgesic drugs: ultrastructural aspects. Acta Pharmacologica Sinica. 2006 Mar;27(3):259-72.\u003c/li\u003e\n \u003cli\u003eWallace JL, Bak A, McKnight W, Asfaha S, Sharkey KA, MacNaughton WK. Cyclooxygenase 1 contributes to inflammatory responses in rats and mice: implications for gastrointestinal toxicity. Gastroenterology. 1998 Jul 1;115(1):101-9.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Sam Global University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"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},"keywords":"NSAIDs, Aspirin, Diclofenac, Paracetamol, Ibuprofen, Disprin, histopathology","lastPublishedDoi":"10.21203/rs.3.rs-8651332/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8651332/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe main objective of this study is to make an assessment of the various types of NSAIDs toxicity on rodents, depending on the amount of the drug used, and with a special focus on tissue architecture. The mice were split into groups of six: group 1 was given normal saline, and group 2,3,4,5 and 6 were given orally through the feeding needle and 1 ml syringe with a single dose of Aspirin, Diclofenac, Paracetamol, Ibuprofen, and Disprin at concentrations of 1 and 2 mg/kg BW, respectively, for 10 days daily. On the 11th day of the experiment, the mice were killed by cervical dislocation. The study found that there was a significant change in BW due to the administration of NSAIDs at all concentrations in comparison with the saline group. The liver was observed as a whole in its cell death that was reversible, with damaged hepatocytes, necrosis, and shrunken central vein. The liver margins were lost due to the death of hepatocytes and the disorientation of the cartwheel arrangement of hepatocytes. When the drugs were given, the liver showed hyperchromatic cells with intermedial dysplastic cells, sinusoidal space marginal increase, and damaged hepatocytes. The kidney showed shrunken Bowman\u0026rsquo;s capsule, medullary rays, enlarged Bowman\u0026rsquo;s capsule, damaged Bowman\u0026rsquo;s capsule, and inflamed Bowman\u0026rsquo;s capsule. The present study concludes that there is a dose-dependent detrimental effect of an intake of NSAIDs and confirmed that, by increasing the concentration of the NSAIDs the toxicity was elevated at the tissue level.\u003c/p\u003e","manuscriptTitle":"Evaluation of the dose-dependent toxicity in different classes of NSAIDs on rodents with special reference to tissue architecture","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-22 10:00:05","doi":"10.21203/rs.3.rs-8651332/v1","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}}],"origin":"","ownerIdentity":"5444c045-2027-499d-a8fc-289942de06c2","owner":[],"postedDate":"January 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":61450497,"name":"Toxicology"}],"tags":[],"updatedAt":"2026-01-22T10:00:06+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-22 10:00:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8651332","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8651332","identity":"rs-8651332","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}