Effect of nanoparticles of tranexamic acid on Intra-Abdominal Adhesion after Laparotomy on rat

Effect of nanoparticles of tranexamic acid on Intra-Abdominal Adhesion after Laparotomy on rat | 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 Effect of nanoparticles of tranexamic acid on Intra-Abdominal Adhesion after Laparotomy on rat Salar Zehforoush, Alireza Jahandideh, MohammadMahdi Alinaghizadeh, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5737190/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 Background :Intra-abdominal adhesions frequently arise as a complication following abdominal surgeries. These adhesions lead to internal scarring as a result of damage to abdominal organs, including the peritoneum. Purpose :This research explores the effects of a Nano-formulated version of tranexamic acid on intra-abdominal adhesions in rats, utilizing both microscopic and macroscopic analysis. Methods : A total of thirty adult male Wistar rats (weighing between 300 and 350 grams) were randomly divided into three treatment groups: a control group, a group receiving Nano-drug tranexamic acid (50 mg/kg), and a group receiving standard tranexamic acid (50 mg/kg). Anesthesia was administered via intramuscular injections of 10% ketamine (50 mg/kg) and 2% xylazine (5 mg/kg) as per established guidelines. Adhesion was induced in all subjects by making incisions in the abdominal wall. On days 14 and 28 post-surgery, all rats underwent a second laparotomy, during which the extent of intra-abdominal adhesions was evaluated through both macroscopic and microscopic inspections. Results :The macroscopic evaluation indicated a marked reduction in the formation of adhesion bands within both the Nano-drug and standard drug treatment groups when compared to the control group (P<0.05). The Nano-drug treatment group exhibited the least amount of adhesion, whereas the control group showed the greatest incidence. Microscopic examination of pathological slides from the adhesion sites revealed that levels of inflammation and fibrotic tissue development were significantly reduced in both treatment groups versus the control group (P<0.05). Conclusions :The Nano-drug group exhibited the lowest levels of inflammation and fibrotic tissue, while the highest levels were recorded in the control group. tranexamic acid Nano particle Abdominal adhesion Laparotomy Rat Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Intra-abdominal adhesions rank among the most common complications after abdominal surgeries, impacting more than 90% of individuals who undergo these procedures, with dire cases potentially resulting in death ( 1 ). Adhesions form when fibrous tissue connects abdominal organs to one another or to the abdominal wall. Although they often present without symptoms, these adhesions can lead to a condition known as adhesive disease. Standard lab tests and imaging methods usually fail to provide a definitive diagnosis for adhesive disease, which may lead to long-lasting issues, such as intermittent blockages in the small intestine. While abdominal surgery is recognized as the main cause of adhesive disease, factors such as infections, inflammation, and radiation treatment can also play a role ( 2 ). Despite considerable investigation, the exact mechanisms behind adhesion formation remain elusive. It is believed that the development of adhesions occurs in three phases: the destruction and rupture of the mesothelial surface, the coagulation of fibrin, and the subsequent inflammatory response. Symptoms associated with adhesive disease can include persistent bloating, abdominal pain, constipation or increased bowel frequency, nausea, indicators of intestinal blockage, and rectal bleeding ( 2 ). Avoiding internal abdominal adhesions can be achieved through three primary approaches: reducing damage to the peritoneum during surgical procedures, using medication to control the production and breakdown of fibrin, and implementing physical barriers to stop organ adhesion within the abdomen ( 3 , 4 ). Tranexamic acid, which resembles lysine in structure, acts as a competitive inhibitor for the conversion of plasminogen into plasmin. This action helps prevent the breakdown of fibrin clots and provides anti-fibrinolytic effects. Its main applications are to avert significant bleeding and lessen the necessity for blood transfusions, while also decreasing inflammatory responses by blocking plasminogen activation ( 5 – 7 ). In recent times, the use of nanoparticles has increased significantly, leading to the development of various medications incorporated within nanomaterial frameworks. These nanoparticles, defined by their tiny dimensions (ranging from 1 to 100 nanometers), high reactivity, and adaptable surface properties, can be delivered through multiple routes including topical applications, subcutaneous injections, oral consumption, direct injections, and inhalation. The pathways for excreting these particles differ based on their size, method of administration, shape, and surface features, with removal generally occurring through the kidneys, liver, or lungs ( 8 , 9 ). Materials and methods This investigation took place at the Faculty of Specialized Veterinary Sciences, Science and Research Branch, in Tehran, Iran, with the endorsement of the Ethics Committee of Islamic Azad University Science and Research Branch (reference No. 1400348). Surgical procedure In this experiment, a total of 30 male Wistar rats, approximately 4 months old and weighing between 300 and 350 grams, were employed. The rats were randomly divided into three equal groups: the first group received a treatment of nano-drug tranexamic acid (50 mg/kg), the second group was treated with standard tranexamic acid (50 mg/kg), and the third group acted as a control, receiving normal saline. Before the surgical procedure, the rats were deprived of food overnight. On the day of surgery, they were anesthetized with an intramuscular injection of 10% ketamine (50 mg/kg) and 2% xylazine (5 mg/kg). For surgical preparation, the midline abdominal area was cleansed thoroughly using povidone-iodine 2.5%. A 3 cm incision was carefully made in the midline, and upon reaching the peritoneal cavity, three 2 cm longitudinal cuts were executed on the right side of the abdominal wall (inner side) using a No. 4 surgical blade to create standard adhesions. Additionally, 2 × 2 cm sections were removed from the inner surface of the left side of the abdominal wall with surgical scissors to promote intra-abdominal adhesion. The abdominal opening was sutured using 3.0 absorbable monofilament Vicryl sutures in a simple interrupted pattern spaced 1 cm apart. The fascia and midline muscles were stitched together with 2.0 absorbable monofilament Vicryl sutures, while the skin was closed with 3.0 non-absorbable monofilament Nylon sutures. Throughout the procedure, the body temperature of the rats was maintained between 36 and 38 °C using a heat lamp. Treatments A total of 30 male Wistar rats were randomly split into three equal groups, and initial surgical procedures were performed on them. The treatment phase lasted for 28 days, beginning on the day the lesions were created. In the first group, after inducing adhesions, a nano-drug known as tranexamic acid (50 mg/kg) was administered through the intraperitoneal route. The second group also received tranexamic acid (50 mg/kg) intraperitoneally, but this occurred after the induction of adhesions. The third group, which served as the control, was given a normal saline solution intraperitoneally following adhesion induction Macroscopic evaluation On the 14th and 28th days after the surgery, another laparotomy was carried out to evaluate the adhesions. The same surgeon conducted this procedure and classified the adhesions based on their findings. Referring to Table 1, each adhesion's severity was evaluated individually and compared against one another (10). Table 1: Scoring and macroscopic categorization of abdominal adhesions in rats (10). Description Score No adhesive bands 0 One thin, non-vascular, easily removable 1 Two non-vascular, easily removable 2 Three non-vascular, easily removable 3 More than 3 non-vascular, easily removable 4 Histopathological evaluation On the 14th and 28th days following the surgery, samples of tissue were taken from the adhered areas and soaked in a 10% formalin solution for a duration of two days. After this, the samples were sliced to a thickness of 4 μm and stained using Harris's hematoxylin along with an alcoholic eosin method to aid in the assessment of the histopathology. The slides that were prepared were scrutinized under a microscope at a magnification of 100x (11, 12). The adhesions were rated individually according to the level of fibrosis and inflammation, adhering to the standards specified in Table 2 (11). Table 2: Criteria for evaluating inflammation histopathologically (11). Severity Degree of inflammation Score No No inflammation 0 Mild Giant, lymphocytes, plasma cells 1 Moderate Giant, plasma cells, eosinophils 2 Severe Inflammatory cell infiltration 3 Data analysis In order to collect data, every rat and sample was given a distinctive number, and a detailed checklist was prepared for each one, documenting all pertinent variables being examined. This included factors like the extent of visible adhesion and various histopathological elements. After gathering the information, the data was processed using GraphPad Prism version 9.00 (GraphPad Software, San Diego, CA), utilizing the Kruskal-Wallis Test for analysis. A significance threshold of P < 0.05 was established, suggesting that the results were statistically significant. This approach facilitated the numerical representation of qualitative observations, such as levels of adhesion, fibrosis, and inflammation. Results Macroscopic examination: Upon conducting a thorough macroscopic assessment on days 14 and 28, there were no indications of fluid accumulation in the abdominal cavity across any of the examined groups. Additionally, throughout the course of treatment, none of the rats showed any signs of infections or blockages in their intestines. The macroscopic analysis carried out on the fourteenth day after surgery indicated that the group receiving the nano-drug tranexamic acid (50 mg/kg) had the least occurrence of abdominal adhesions. In stark contrast, the control group displayed the highest prevalence of such adhesions. A noteworthy distinction in the formation of intra-abdominal adhesions was evident when comparing the control group to those treated with the nano-drug tranexamic acid, with a statistical significance of P < 0.05. Values are given as mean ± SEM ( n =10). Data analyzed by Kruskal-Wallis and Mann-Whitney U tests. A different letters in each column indicate statistically significant difference ( P 0.9999 Nano drug vs. Control -16.65 **** <0.0001 Drug vs. Control -13.05 ** 0.0015 Values are given as mean ± SEM ( n =10). Data analyzed by Kruskal-Wallis and Mann-Whitney U tests. A different letters in each column indicate statistically significant difference ( P 0.9999 Nano drug vs. Control -16.05 **** <0.0001 Drug vs. Control -12.90 ** 0.0016 Microscopic examination: On the 14th day following surgery, the examination of tissue samples revealed that the group receiving the nano-formulation of tranexamic acid (50 mg/kg) showed the least amount of inflammation, whereas the control group recorded the most. A notable distinction was found when comparing the control group to those treated with either the nano-drug or the tranexamic acid (P < 0.05). Additionally, an analysis of the fibrosis index on day 14 post-surgery indicated that both the nano-drug tranexamic acid (50 mg/kg) and the standard tranexamic acid (50 mg/kg) groups demonstrated the lowest levels of fibrosis. In stark contrast, the control group had the highest fibrosis index. Again, there was a significant difference between the control and the treatment groups (P < 0.05). Values are given as mean ± SEM ( n =10). Data analyzed by Kruskal-Wallis and Mann-Whitney U tests. A different letters in each column indicate statistically significant difference ( P 0.9999 Nano drug vs. Control -10.50 * 0.0114 Drug vs. Control -8.400 Ns 0.0617 Inflammation Nano drug vs. Drug -6.100 Ns 0.3288 Nano drug vs. Control -17.60 **** <0.0001 Drug vs. Control -11.50 ** 0.0077 The histopathological analysis conducted on the 28th day showed results comparable to those from the 14th day. Notably, the groups that received treatment with the nano-drug and tranexamic acid (at a dosage of 50 mg/kg) presented the least amount of inflammation and fibrosis index. In contrast, the control group revealed the highest levels of both inflammation and fibrosis. Furthermore, a marked distinction was observed between the control group and the two groups that received treatment. Values are given as mean ± SEM ( n =10). Data analysed by Kruskal-Wallis and Mann-Whitney U tests. A different letters in each column indicate statistically significant difference ( P <0.05). Table 6: Statistical comparison of inflammation and fibrosis index between all groups on day 28 Fibrosis Groups Mean rank diff. Significant Adjusted P Value Nano drug vs. Drug -4.350 ns 0.6985 Nano drug vs. Control -15.30 **** 0.9999 Nano drug vs. Control -16.00 **** <0.0001 Drug vs. Control -13.10 ** 0.0011 Discussion The goal of this research was to explore how tranexamic acid nanoparticles influence the reduction of adhesions resulting from laparotomy procedures. The visual assessment of the treatment groups indicated that the group receiving nano-formulated tranexamic acid (50 mg/kg) experienced a marked decrease in adhesions compared to the control group. Furthermore, the histopathological analysis of samples taken from adhesion sites demonstrated significantly reduced inflammatory responses and less fibrotic tissue development in the group treated with nano-drug tranexamic acid (50 mg/kg) relative to the control. Intra-abdominal adhesions are frequent complications that impact more than half of abdominal surgery patients, leading to various post-operative issues, such as small intestine obstructions, chronic abdominal discomfort, and infertility in women. These adhesions often go unnoticed and are difficult to identify through standard imaging and laboratory techniques ( 1 , 2 ). Research indicates that adhesions occur in 95% of individuals who have undergone laparotomy, arising from procedures like gastrointestinal surgery, hysterectomy, ectopic pregnancy treatment, as well as liver and gallbladder surgeries. In the last ten years, numerous strategies have been assessed to minimize adhesion formation after abdominal operations, including the application of coagulants, fibrinolytic agents, anti-inflammatory medications, antibiotics, and physical barriers ( 13 ). Tranexamic acid, a synthetic analog of the amino acid lysine, has properties that prevent the breakdown of blood clots, making it useful in minimizing blood loss and the necessity for blood transfusions in patients undergoing surgery. This medication can be given through various methods, including intravenous, intra-articular, oral, topical, or in conjunction with other treatments ( 5 , 6 ). Research has explored the effectiveness of combining tranexamic acid with substances like gelatin to better control internal bleeding ( 14 ). In a study by Topal et al. (2010), the effectiveness of antifibrinolytic medications in reducing postoperative adhesions was showcased. Their research indicated that tissue plasminogen activator (tPA), fondaparinux sodium (FS), and activated drotrecogin alfa (ADA) significantly lowered the formation of adhesions after laparotomy procedures in rats ( 15 ). Our results support previous findings by Togal et al. regarding the role of antifibrinolytic agents in minimizing postoperative adhesions. The decrease in adhesion formation following tranexamic acid treatment is likely due to its capacity to inhibit fibrinolysis and reduce inflammation, which aids the healing process. Additionally, while Smith et al. (2017) showed that administering tranexamic acid can lead to less bleeding and a reduced likelihood of needing a blood transfusion, there are concerns about the risk of developing blood clots, stroke, and heart attacks. Nevertheless, studies indicate that patients receiving tranexamic acid during heart surgery may face a lower risk of such complications compared to those who do not receive it ( 16 ). Considering these potential risks, applying tranexamic acid locally is often regarded as a better option than systemic use. Intraperitoneal bleeding is a well-known risk factor for the formation of postoperative adhesions. By effectively managing bleeding and preventing blood from pooling in the abdominal cavity, our results are consistent with existing research that shows a decrease in post-surgical inflammation and adhesion development. This finding is in agreement with a meta-analysis conducted by Koh et al. in 2021, which reviewed 19 randomized controlled trials and found that tranexamic acid (TXA) significantly reduced blood loss during surgery and the necessity for blood transfusions in extrahepatic abdominal procedures, without raising the risk of thromboembolic complications( 17 ). In our research, we noted that the intraperitoneal administration of nano-tranexamic acid led to a marked reduction in post-operative inflammation, fibrosis, and adhesions in a rat model undergoing laparoscopic surgery. This supports the conclusions of Wang's 2018 study, which indicated that intramuscular injections of three doses of tranexamic acid before and after surgery significantly lowered bleeding, inflammation, and discomfort ( 18 ). The employment of nano-tranexamic acid has numerous benefits, including improved absorption and targeted delivery to the injury site. The reduction in post-operative complications can be linked to the well-documented anti-fibrinolytic effects of tranexamic acid. By inhibiting the breakdown of fibrin, tranexamic acid helps maintain blood clots, decrease blood loss, and lessen the inflammatory response. In a 2010 study by David M. Wiseman and his team, they examined the impact of a fibrin-based product containing tranexamic acid (Adhexil) on preventing adhesions in the uterine horn of rabbits. Their findings showed that in models with uterine adhesions to the peritoneal cavity, using Adhexil significantly diminished both the severity and occurrence of adhesions ( 19 ). These outcomes support our research, reinforcing the idea that compounds containing tranexamic acid are effective in minimizing peritoneal adhesions. Our results are consistent with earlier studies that highlight the effectiveness of TXA in minimizing intra-abdominal adhesions. A 2004 investigation led by David M. Wiseman and his team involving 228 male rats revealed that the incorporation of TXA into a fibrin sealant notably lowered both the occurrence and intensity of adhesions post-laparotomy ( 20 ). We noted comparable outcomes in our research, especially within the nano-TXA group during the 28-day evaluation period. The application of nanoscience in this study illustrates the increasing inclination towards employing cutting-edge technologies for drug delivery. Nanoparticles exhibit distinct biological and chemical characteristics that can enhance the availability of drugs, diminish toxicity, and boost therapeutic outcomes. When it comes to preventing adhesions, nanoparticles have the potential to improve penetration into the peritoneal cavity and ensure localized delivery of TXA to areas prone to adhesion formation. In conclusion, administering nano-tranexamic acid at a dosage of 50 mg/kg directly in the affected area leads to a significant reduction in intra-abdominal adhesions following laparotomy. Furthermore, this substance also mitigates inflammatory responses and the formation of fibrotic tissue at the site where adhesions are induced. Declarations Conflict of Interest The authors declare there is no conflict of interest. Funding This research was not funded by any organization. Author Contribution Salar Zehforoush: planingAlireza Jahandideh:Corresponding authorsMohammadMahdi Alinaghizadeh:data analysis Hamed Karimi: sampling Acknowledgement The authors thank Vice President of Research and Technology, Shahid Bahonar University of Kerman, Iran Data Availability All of the data are available at Faculty of Veterinary Medicine , Shahid Bahonar University of Kerman, Iran References Jahandideh, Alireza, Gholamreza Abedi, and Abolfazl Akbarzadeh. "Histopathological assessment of nano n-acetyl cysteine effect on postoperative adhesion in rats." Iraqi Journal of Veterinary Sciences 35.3 (2021): 589-597. Tabibian, N., et al. (2017). "Abdominal adhesions: A practical review of an often overlooked entity." Annals of Medicine and Surgery 15: 9-13. Ellis, H., et al. (1999). "Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study." The Lancet 353(9163): 1476-1480. Iwasaki, K., et al. (2019). "Pharmacological mobilization and recruitment of stem cells in rats stops abdominal adhesions after laparotomy." Scientific reports 9(1): 1-8 Wang, D., et al. (2018). "The antifibrinolytic and anti‐inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial." Journal of Thrombosis and Haemostasis 16(12): 2442-2453. Ng, W. C. K., et al. (2015). "Tranexamic acid: a clinical review." Anaesthesiology intensive therapy 47(4): 339-350. Ker, K., et al. (2012). "Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis." Bmj 344. Bose, T., et al. (2014). "Overview of nano-drugs characteristics for clinical application: the journey from the entry to the exit point." Journal of nanoparticle research 16(8): 1-25. Nikolić, V., et al. (2019). Administration routes for nano drugs and characterization of nano drug loading. Characterization and biology of nanomaterials for drug delivery, Elsevier: 587-625. Lorenz, E., et al. (1997). Pathophysiology and classification of adhesions. Peritoneal adhesions, Springer: 29-34 Parsaei, P., et al. (2013). "Bioactive components and preventive effect of green tea (Camellia sinensis) extract on post-laparotomy intra-abdominal adhesion in rats." International Journal of Surgery 11(9): 811-815 Atarbashe, R. K. and A. Abu-Raghif (2020). "Comparative treatment of induced ulcerative colitis in male rat model by using cinnarizine and sulfasalazine." Iraqi Journal of Veterinary Sciences 34(2): 465-472. Diamond, M. P., et al. (2011). "A prospective, controlled, randomized, multicenter, exploratory pilot study evaluating the safety and potential trends in efficacy of Adhexil." Fertility and sterility 95(3): 1086-1090. Sezer, U. A., et al. (2016). "Combination of gelatin and tranexamic acid offers improved haemostasis and safe use on internal hemorrhage control." RSC advances 6(97): 95189-95198. Topal E, Ozturk E, Şen G, Yerci O, Yılmazlar T. A Comparison of Three Fibrinolytic Agents in Prevention of Intra-Abdominal Adhesions. Acta Chir Belg [Internet]. 2010;110:71–5. Available from: https://api.semanticscholar.org/CorpusID:23351061 Smith, J. A., et al. (2017). "Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery." Koh A, Adiamah A, Sanyal S. 842 Safety and Efficacy of Tranexamic Acid to Minimise Perioperative Bleeding in Extrahepatic Abdominal Surgery: A Systematic Review. Br J Surg [Internet]. 2021;108. Available from: https://api.semanticscholar.org/CorpusID:236578483 Wang D, Luo Z-Y, Yu Z-P, Liu L-X, Chen C, Meng W-K, et al. The antifibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial. J Thromb Haemost. 2018 Dec;16(12):2442–53. Wiseman DM, Meidler R, Lyahovetsky Y, Kurman E, Horn S, Nur I. Evaluation of a fibrin preparation containing tranexamic acid (Adhexil) in a rabbit uterine horn model of adhesions with and without bleeding and in a model with two surgical loci. Fertil Steril. 2010 Mar;93(4):1045–51. Wiseman DM, Lyachovetsky Y, Keidan I, Trout JR, Nur I. The effect of tranexamic acid in fibrin sealant on adhesion formation in the rat. J Biomed Mater Res B Appl Biomater [Internet]. 2004;68 2:222–30. Available from: https://api.semanticscholar.org/CorpusID:37646051 Additional Declarations No competing interests reported. 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. 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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-5737190","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":396156493,"identity":"c5a9982b-b137-40fc-bb7a-3031f21a127e","order_by":0,"name":"Salar Zehforoush","email":"","orcid":"","institution":"Shahid Bahonar University of Kerman","correspondingAuthor":false,"prefix":"","firstName":"Salar","middleName":"","lastName":"Zehforoush","suffix":""},{"id":396156494,"identity":"1ecfc265-a850-483e-afce-ddf5331742fd","order_by":1,"name":"Alireza Jahandideh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYBAC9gYeIMkmwdggwXyAAUhCxQ1wa2FEaGFLIEkLSDGPAZAkwmGM7WcPfi4os5Dtl+75/Llyh4W8wQHmhx8YCu7h1tKTlyw945yE8cw5Z7dJnj0jYbjhAJuxBINBMR6H5RhI87ZJJG64kbuNsbFNgnHDAQYzoF8ScGvpf2P8G6Rl/42cxx+BWuw3HGD/hleL4IwcM4gtEjkMko0gxgEe/LZIS7wxs+YB+mXGjTQzycYzEskzD/MUSyTg0cLHn2N8m6esTrZ/RjLQYTvqbPuOt2/88OEPbi1YADMQk6RhFIyCUTAKRgEGAADcvVHUclFljAAAAABJRU5ErkJggg==","orcid":"","institution":"Islamic Azad University, Tehran","correspondingAuthor":true,"prefix":"","firstName":"Alireza","middleName":"","lastName":"Jahandideh","suffix":""},{"id":396156495,"identity":"5feb1480-2ced-4f2b-9e31-ec7120f1f664","order_by":2,"name":"MohammadMahdi Alinaghizadeh","email":"","orcid":"","institution":"Shahid Bahonar University of Kerman","correspondingAuthor":false,"prefix":"","firstName":"MohammadMahdi","middleName":"","lastName":"Alinaghizadeh","suffix":""},{"id":396156496,"identity":"e1c4a785-4437-4ff3-bce1-080e02dca711","order_by":3,"name":"Hamed Karimi","email":"","orcid":"","institution":"Shahid Bahonar University of Kerman","correspondingAuthor":false,"prefix":"","firstName":"Hamed","middleName":"","lastName":"Karimi","suffix":""}],"badges":[],"createdAt":"2024-12-30 17:38:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5737190/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5737190/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72795921,"identity":"20c2cd6c-2c62-4809-8b73-7287a932e10b","added_by":"auto","created_at":"2025-01-02 08:59:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":19373,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of Nano drug and Drug on macroscopic examination of adhesion in treatment and control groups on day 14.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5737190/v1/c7f7331ca810472bfe62a95a.png"},{"id":72798835,"identity":"4d930715-c4f0-45dc-ad21-a22a5c68b4ee","added_by":"auto","created_at":"2025-01-02 09:15:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":922577,"visible":true,"origin":"","legend":"\u003cp\u003eMacroscopic image of Nano drug tranexamic acid (50 mg) group on day 14, with no adhesions (A). Macroscopic image of Nano drug tranexamic acid (50 mg) group on day 28, with no adhesions (B). Macroscopic image of tranexamic acid drug (50 mg) group on day 14, with low adhesion (C). Macroscopic image of tranexamic acid drug (50 mg) group on day 28, with no adhesions (D). Macroscopic image of control group on day 14, with severe adhesions (E). Macroscopic image of control group on day 28, with severe adhesions (F).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5737190/v1/f923e9519a0ef784499265f5.png"},{"id":72795922,"identity":"bcc07bb0-0ea2-49e4-9f82-e8346aede6a0","added_by":"auto","created_at":"2025-01-02 08:59:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":17144,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 8: The effect of Nano drug and Drug on macroscopic examination of adhesion in treatment and control groups on day 28.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5737190/v1/14f9513a0a60b85820a12660.png"},{"id":72795928,"identity":"53f8f82f-a8c2-4004-839e-53e939738a7b","added_by":"auto","created_at":"2025-01-02 08:59:55","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1066638,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 3. Microscopic section from the abdominal wall, on day 14 post-operation, in the Nano drug tranexamic acid group , shows Low penetration of fibrotic tissue ( arrowhead ) and mild inflammation ( arrow ) (H\u0026amp;E, 10X) (A), Microscopic section from the abdominal wall, on day 28 post-operation, in the Nano drug tranexamic acid group , shows mild fibrotic tissue formation (H\u0026amp;E, 10X) (B), Microscopic section from the abdominal wall, on day 14 post-operation, in the tranexamic acid drug group , shows Moderate infiltration of fibrotic tissue ( arrowhead ) and low inflammation ( arrow ) (H\u0026amp;E, 10X) (C), Microscopic section from the abdominal wall, on day 28 post-operation, in the tranexamic acid drug group , shows low inflammation ( arrow ) and moderate fibrosis ( arrowhead) (H\u0026amp;E, 40X) (D), Microscopic section from the abdominal wall, on day 14 post-operation, in the Control group , shows Severe infiltration of fibrotic connective tissue ( arrowhead ) (H\u0026amp;E, 10X) (E), Microscopic section from the abdominal wall, on day 28 post-operation, in the Control group , shows severe infiltration of fibrotic tissue ( arrowhead ) (H\u0026amp;E, 10X) (F).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5737190/v1/eb290cd527f6d63a4f6d7081.png"},{"id":72796779,"identity":"dcf9bf47-3a05-42f6-8b5a-3edfd31ab93a","added_by":"auto","created_at":"2025-01-02 09:07:55","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":37307,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 9: The effect of Nano drug and Drug on macroscopic examination of inflammation and fibrosis index in treatment and control groups on day 14.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-5737190/v1/8a0a6c94a55f33da1b06d4d5.png"},{"id":72796781,"identity":"5ccb2e84-f0dc-4a52-b765-8dee3eb1b858","added_by":"auto","created_at":"2025-01-02 09:07:55","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":31159,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 10: The effect of Nano drug and Drug on macroscopic examination of inflammation and fibrosis index in treatment and control groups on day 28.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-5737190/v1/21b3a13872113ffcc2d1f282.png"},{"id":74687344,"identity":"9838a405-9b37-4327-a7f7-bfa303cb1acd","added_by":"auto","created_at":"2025-01-24 17:16:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3021036,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5737190/v1/69637288-5546-49e0-88ef-7cb0a89414eb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of nanoparticles of tranexamic acid on Intra-Abdominal Adhesion after Laparotomy on rat","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIntra-abdominal adhesions rank among the most common complications after abdominal surgeries, impacting more than 90% of individuals who undergo these procedures, with dire cases potentially resulting in death (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Adhesions form when fibrous tissue connects abdominal organs to one another or to the abdominal wall. Although they often present without symptoms, these adhesions can lead to a condition known as adhesive disease. Standard lab tests and imaging methods usually fail to provide a definitive diagnosis for adhesive disease, which may lead to long-lasting issues, such as intermittent blockages in the small intestine. While abdominal surgery is recognized as the main cause of adhesive disease, factors such as infections, inflammation, and radiation treatment can also play a role (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Despite considerable investigation, the exact mechanisms behind adhesion formation remain elusive. It is believed that the development of adhesions occurs in three phases: the destruction and rupture of the mesothelial surface, the coagulation of fibrin, and the subsequent inflammatory response. Symptoms associated with adhesive disease can include persistent bloating, abdominal pain, constipation or increased bowel frequency, nausea, indicators of intestinal blockage, and rectal bleeding (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAvoiding internal abdominal adhesions can be achieved through three primary approaches: reducing damage to the peritoneum during surgical procedures, using medication to control the production and breakdown of fibrin, and implementing physical barriers to stop organ adhesion within the abdomen (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTranexamic acid, which resembles lysine in structure, acts as a competitive inhibitor for the conversion of plasminogen into plasmin. This action helps prevent the breakdown of fibrin clots and provides anti-fibrinolytic effects. Its main applications are to avert significant bleeding and lessen the necessity for blood transfusions, while also decreasing inflammatory responses by blocking plasminogen activation (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn recent times, the use of nanoparticles has increased significantly, leading to the development of various medications incorporated within nanomaterial frameworks. These nanoparticles, defined by their tiny dimensions (ranging from 1 to 100 nanometers), high reactivity, and adaptable surface properties, can be delivered through multiple routes including topical applications, subcutaneous injections, oral consumption, direct injections, and inhalation. The pathways for excreting these particles differ based on their size, method of administration, shape, and surface features, with removal generally occurring through the kidneys, liver, or lungs (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eThis investigation took place at the Faculty of Specialized Veterinary Sciences, Science and Research Branch, in Tehran, Iran, with the endorsement of the Ethics Committee of Islamic Azad University Science and Research Branch (reference No. 1400348).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgical procedure\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this experiment, a total of 30 male Wistar rats, approximately 4 months old and weighing between 300 and 350 grams, were employed. The rats were randomly divided into three equal groups: the first group received a treatment of nano-drug tranexamic acid (50 mg/kg), the second group was treated with standard tranexamic acid (50 mg/kg), and the third group acted as a control, receiving normal saline.\u003c/p\u003e\n\u003cp\u003eBefore the surgical procedure, the rats were deprived of food overnight. On the day of surgery, they were anesthetized with an intramuscular injection of 10% ketamine (50 mg/kg) and 2% xylazine (5 mg/kg). For surgical preparation, the midline abdominal area was cleansed thoroughly using povidone-iodine 2.5%. A 3 cm incision was carefully made in the midline, and upon reaching the peritoneal cavity, three 2 cm longitudinal cuts were executed on the right side of the abdominal wall (inner side) using a No. 4 surgical blade to create standard adhesions. Additionally, 2 \u0026times; 2 cm sections were removed from the inner surface of the left side of the abdominal wall with surgical scissors to promote intra-abdominal adhesion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe abdominal opening was sutured using 3.0 absorbable monofilament Vicryl sutures in a simple interrupted pattern spaced 1 cm apart. The fascia and midline muscles were stitched together with 2.0 absorbable monofilament Vicryl sutures, while the skin was closed with 3.0 non-absorbable monofilament Nylon sutures. Throughout the procedure, the body temperature of the rats was maintained between 36 and 38 \u0026deg;C using a heat lamp.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 30 male Wistar rats were randomly split into three equal groups, and initial surgical procedures were performed on them. The treatment phase lasted for 28 days, beginning on the day the lesions were created. In the first group, after inducing adhesions, a nano-drug known as tranexamic acid (50 mg/kg) was administered through the intraperitoneal route. The second group also received tranexamic acid (50 mg/kg) intraperitoneally, but this occurred after the induction of adhesions. The third group, which served as the control, was given a normal saline solution intraperitoneally following adhesion induction\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMacroscopic evaluation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn the 14th and 28th days after the surgery, another laparotomy was carried out to evaluate the adhesions. The same surgeon conducted this procedure and classified the adhesions based on their findings. Referring to Table 1, each adhesion\u0026apos;s severity was evaluated individually and compared against one another (10). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 1: Scoring and macroscopic categorization of abdominal adhesions in rats (10).\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1506%;\"\u003e\n \u003cp dir=\"LTR\"\u003eDescription\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8494%;\"\u003e\n \u003cp dir=\"LTR\"\u003eScore\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1506%;\"\u003e\n \u003cp dir=\"LTR\"\u003eNo adhesive bands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8494%;\"\u003e\n \u003cp dir=\"LTR\"\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1506%;\"\u003e\n \u003cp dir=\"LTR\"\u003eOne thin, non-vascular, easily removable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8494%;\"\u003e\n \u003cp dir=\"LTR\"\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1506%;\"\u003e\n \u003cp dir=\"LTR\"\u003eTwo non-vascular, easily removable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8494%;\"\u003e\n \u003cp dir=\"LTR\"\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1506%;\"\u003e\n \u003cp dir=\"LTR\"\u003eThree non-vascular, easily removable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8494%;\"\u003e\n \u003cp dir=\"LTR\"\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 76.1506%;\"\u003e\n \u003cp dir=\"LTR\"\u003eMore than 3 non-vascular, easily removable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.8494%;\"\u003e\n \u003cp dir=\"LTR\"\u003e4\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\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistopathological evaluation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn the 14th and 28th days following the surgery, samples of tissue were taken from the adhered areas and soaked in a 10% formalin solution for a duration of two days. After this, the samples were sliced to a thickness of 4 \u0026mu;m and stained using Harris\u0026apos;s hematoxylin along with an alcoholic eosin method to aid in the assessment of the histopathology. The slides that were prepared were scrutinized under a microscope at a magnification of 100x (11, 12). The adhesions were rated individually according to the level of fibrosis and inflammation, adhering to the standards specified in Table 2 (11).\u003c/p\u003e\n\u003cp\u003eTable 2: Criteria for evaluating inflammation histopathologically (11).\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.3333%;\"\u003e\n \u003cp dir=\"LTR\"\u003eSeverity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52.514%;\"\u003e\n \u003cp dir=\"LTR\"\u003eDegree of inflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1527%;\"\u003e\n \u003cp dir=\"LTR\"\u003eScore\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.3333%;\"\u003e\n \u003cp dir=\"LTR\"\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52.514%;\"\u003e\n \u003cp dir=\"LTR\"\u003eNo inflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1527%;\"\u003e\n \u003cp dir=\"LTR\"\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.3333%;\"\u003e\n \u003cp dir=\"LTR\"\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52.514%;\"\u003e\n \u003cp dir=\"LTR\"\u003eGiant, lymphocytes, plasma cells\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1527%;\"\u003e\n \u003cp dir=\"LTR\"\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.3333%;\"\u003e\n \u003cp dir=\"LTR\"\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52.514%;\"\u003e\n \u003cp dir=\"LTR\"\u003eGiant, plasma cells, eosinophils\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1527%;\"\u003e\n \u003cp dir=\"LTR\"\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33.3333%;\"\u003e\n \u003cp dir=\"LTR\"\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52.514%;\"\u003e\n \u003cp dir=\"LTR\"\u003eInflammatory cell infiltration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1527%;\"\u003e\n \u003cp dir=\"LTR\"\u003e3\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\u003eData analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn order to collect data, every rat and sample was given a distinctive number, and a detailed checklist was prepared for each one, documenting all pertinent variables being examined. This included factors like the extent of visible adhesion and various histopathological elements. After gathering the information, the data was processed using GraphPad Prism version 9.00 (GraphPad Software, San Diego, CA), utilizing the Kruskal-Wallis Test for analysis. A significance threshold of P \u0026lt; 0.05 was established, suggesting that the results were statistically significant. This approach facilitated the numerical representation of qualitative observations, such as levels of adhesion, fibrosis, and inflammation.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eMacroscopic examination:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUpon conducting a thorough macroscopic assessment on days 14 and 28, there were no indications of fluid accumulation in the abdominal cavity across any of the examined groups. Additionally, throughout the course of treatment, none of the rats showed any signs of infections or blockages in their intestines. The macroscopic analysis carried out on the fourteenth day after surgery indicated that the group receiving the nano-drug tranexamic acid (50 mg/kg) had the least occurrence of abdominal adhesions. In stark contrast, the control group displayed the highest prevalence of such adhesions. A noteworthy distinction in the formation of intra-abdominal adhesions was evident when comparing the control group to those treated with the nano-drug tranexamic acid, with a statistical significance of P \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003eValues are given as mean \u0026plusmn; SEM (\u003cem\u003en\u003c/em\u003e=10). Data analyzed by Kruskal-Wallis and Mann-Whitney U tests. A different letters in each column indicate statistically significant difference (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003eTable 3: Statistical comparison of adhesion between all groups on day 14\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"561\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eMean rank diff.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eSignificant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eAdjusted P Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-3.600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ens\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026gt;0.9999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-16.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e****\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDrug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-13.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues are given as mean \u0026plusmn; SEM (\u003cem\u003en\u003c/em\u003e=10). Data analyzed by Kruskal-Wallis and Mann-Whitney U tests. A different letters in each column indicate statistically significant difference (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003eTable 4: Statistical comparison of adhesion between all groups on day 28\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"546\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 202px;\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eMean rank diff.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eSignificant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eAdjusted P Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-3.150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ens\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026gt;0.9999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-16.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e****\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDrug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-12.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0016\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eMicroscopic examination:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn the 14th day following surgery, the examination of tissue samples revealed that the group receiving the nano-formulation of tranexamic acid (50 mg/kg) showed the least amount of inflammation, whereas the control group recorded the most. A notable distinction was found when comparing the control group to those treated with either the nano-drug or the tranexamic acid (P \u0026lt; 0.05). Additionally, an analysis of the fibrosis index on day 14 post-surgery indicated that both the nano-drug tranexamic acid (50 mg/kg) and the standard tranexamic acid (50 mg/kg) groups demonstrated the lowest levels of fibrosis. In stark contrast, the control group had the highest fibrosis index. Again, there was a significant difference between the control and the treatment groups (P \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003eValues are given as mean \u0026plusmn; SEM (\u003cem\u003en\u003c/em\u003e=10). Data analyzed by Kruskal-Wallis and Mann-Whitney U tests. A different letters in each column indicate statistically significant difference (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003eTable 5: Statistical comparison of inflammation and fibrosis index between all groups on day 14\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 92px;\"\u003e\n \u003cp\u003eFibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eMean rank diff.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eSignificant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eAdjusted P Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-2.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026gt;0.9999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-10.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0114\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDrug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-8.400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0617\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eInflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-6.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.3288\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-17.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e****\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDrug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-11.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0077\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe histopathological analysis conducted on the 28th day showed results comparable to those from the 14th day. Notably, the groups that received treatment with the nano-drug and tranexamic acid (at a dosage of 50 mg/kg) presented the least amount of inflammation and fibrosis index. In contrast, the control group revealed the highest levels of both inflammation and fibrosis. Furthermore, a marked distinction was observed between the control group and the two groups that received treatment.\u003c/p\u003e\n\u003cp\u003eValues are given as mean \u0026plusmn; SEM (\u003cem\u003en\u003c/em\u003e=10). Data analysed by Kruskal-Wallis and Mann-Whitney U tests. A different letters in each column indicate statistically significant difference (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003eTable 6: Statistical comparison of\u0026nbsp;inflammation and fibrosis index between all groups on day 28\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 92px;\"\u003e\n \u003cp\u003eFibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eMean rank diff.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eSignificant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eAdjusted P Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-4.350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ens\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.6985\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-15.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e****\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDrug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-10.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0080\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eInflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-2.900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ens\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026gt;0.9999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNano drug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-16.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e****\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDrug vs. Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-13.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe goal of this research was to explore how tranexamic acid nanoparticles influence the reduction of adhesions resulting from laparotomy procedures. The visual assessment of the treatment groups indicated that the group receiving nano-formulated tranexamic acid (50 mg/kg) experienced a marked decrease in adhesions compared to the control group. Furthermore, the histopathological analysis of samples taken from adhesion sites demonstrated significantly reduced inflammatory responses and less fibrotic tissue development in the group treated with nano-drug tranexamic acid (50 mg/kg) relative to the control.\u003c/p\u003e \u003cp\u003eIntra-abdominal adhesions are frequent complications that impact more than half of abdominal surgery patients, leading to various post-operative issues, such as small intestine obstructions, chronic abdominal discomfort, and infertility in women. These adhesions often go unnoticed and are difficult to identify through standard imaging and laboratory techniques (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eResearch indicates that adhesions occur in 95% of individuals who have undergone laparotomy, arising from procedures like gastrointestinal surgery, hysterectomy, ectopic pregnancy treatment, as well as liver and gallbladder surgeries. In the last ten years, numerous strategies have been assessed to minimize adhesion formation after abdominal operations, including the application of coagulants, fibrinolytic agents, anti-inflammatory medications, antibiotics, and physical barriers (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTranexamic acid, a synthetic analog of the amino acid lysine, has properties that prevent the breakdown of blood clots, making it useful in minimizing blood loss and the necessity for blood transfusions in patients undergoing surgery. This medication can be given through various methods, including intravenous, intra-articular, oral, topical, or in conjunction with other treatments (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Research has explored the effectiveness of combining tranexamic acid with substances like gelatin to better control internal bleeding (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn a study by Topal et al. (2010), the effectiveness of antifibrinolytic medications in reducing postoperative adhesions was showcased. Their research indicated that tissue plasminogen activator (tPA), fondaparinux sodium (FS), and activated drotrecogin alfa (ADA) significantly lowered the formation of adhesions after laparotomy procedures in rats (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Our results support previous findings by Togal et al. regarding the role of antifibrinolytic agents in minimizing postoperative adhesions. The decrease in adhesion formation following tranexamic acid treatment is likely due to its capacity to inhibit fibrinolysis and reduce inflammation, which aids the healing process.\u003c/p\u003e \u003cp\u003eAdditionally, while Smith et al. (2017) showed that administering tranexamic acid can lead to less bleeding and a reduced likelihood of needing a blood transfusion, there are concerns about the risk of developing blood clots, stroke, and heart attacks. Nevertheless, studies indicate that patients receiving tranexamic acid during heart surgery may face a lower risk of such complications compared to those who do not receive it (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Considering these potential risks, applying tranexamic acid locally is often regarded as a better option than systemic use.\u003c/p\u003e \u003cp\u003eIntraperitoneal bleeding is a well-known risk factor for the formation of postoperative adhesions. By effectively managing bleeding and preventing blood from pooling in the abdominal cavity, our results are consistent with existing research that shows a decrease in post-surgical inflammation and adhesion development. This finding is in agreement with a meta-analysis conducted by Koh et al. in 2021, which reviewed 19 randomized controlled trials and found that tranexamic acid (TXA) significantly reduced blood loss during surgery and the necessity for blood transfusions in extrahepatic abdominal procedures, without raising the risk of thromboembolic complications(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our research, we noted that the intraperitoneal administration of nano-tranexamic acid led to a marked reduction in post-operative inflammation, fibrosis, and adhesions in a rat model undergoing laparoscopic surgery. This supports the conclusions of Wang's 2018 study, which indicated that intramuscular injections of three doses of tranexamic acid before and after surgery significantly lowered bleeding, inflammation, and discomfort (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The employment of nano-tranexamic acid has numerous benefits, including improved absorption and targeted delivery to the injury site. The reduction in post-operative complications can be linked to the well-documented anti-fibrinolytic effects of tranexamic acid. By inhibiting the breakdown of fibrin, tranexamic acid helps maintain blood clots, decrease blood loss, and lessen the inflammatory response.\u003c/p\u003e \u003cp\u003eIn a 2010 study by David M. Wiseman and his team, they examined the impact of a fibrin-based product containing tranexamic acid (Adhexil) on preventing adhesions in the uterine horn of rabbits. Their findings showed that in models with uterine adhesions to the peritoneal cavity, using Adhexil significantly diminished both the severity and occurrence of adhesions (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). These outcomes support our research, reinforcing the idea that compounds containing tranexamic acid are effective in minimizing peritoneal adhesions.\u003c/p\u003e \u003cp\u003eOur results are consistent with earlier studies that highlight the effectiveness of TXA in minimizing intra-abdominal adhesions. A 2004 investigation led by David M. Wiseman and his team involving 228 male rats revealed that the incorporation of TXA into a fibrin sealant notably lowered both the occurrence and intensity of adhesions post-laparotomy (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). We noted comparable outcomes in our research, especially within the nano-TXA group during the 28-day evaluation period.\u003c/p\u003e \u003cp\u003eThe application of nanoscience in this study illustrates the increasing inclination towards employing cutting-edge technologies for drug delivery. Nanoparticles exhibit distinct biological and chemical characteristics that can enhance the availability of drugs, diminish toxicity, and boost therapeutic outcomes. When it comes to preventing adhesions, nanoparticles have the potential to improve penetration into the peritoneal cavity and ensure localized delivery of TXA to areas prone to adhesion formation.\u003c/p\u003e \u003cp\u003eIn conclusion, administering nano-tranexamic acid at a dosage of 50 mg/kg directly in the affected area leads to a significant reduction in intra-abdominal adhesions following laparotomy. Furthermore, this substance also mitigates inflammatory responses and the formation of fibrotic tissue at the site where adhesions are induced.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of Interest\u003c/h2\u003e \u003cp\u003eThe authors declare there is no conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research was not funded by any organization.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eSalar Zehforoush: planingAlireza Jahandideh:Corresponding authorsMohammadMahdi Alinaghizadeh:data analysis Hamed Karimi: sampling\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors thank Vice President of Research and Technology, Shahid Bahonar University of Kerman, Iran\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll of the data are available at Faculty of Veterinary Medicine , Shahid Bahonar University of Kerman, Iran\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJahandideh, Alireza, Gholamreza Abedi, and Abolfazl Akbarzadeh. \u0026quot;Histopathological assessment of nano n-acetyl cysteine effect on postoperative adhesion in rats.\u0026quot; \u003cem\u003eIraqi Journal of Veterinary Sciences\u003c/em\u003e 35.3 (2021): 589-597.\u003c/li\u003e\n\u003cli\u003eTabibian, N., et al. (2017). \u0026quot;Abdominal adhesions: A practical review of an often overlooked entity.\u0026quot; Annals of Medicine and Surgery 15: 9-13.\u003c/li\u003e\n\u003cli\u003eEllis, H., et al. (1999). \u0026quot;Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study.\u0026quot; The Lancet 353(9163): 1476-1480.\u003c/li\u003e\n\u003cli\u003eIwasaki, K., et al. (2019). \u0026quot;Pharmacological mobilization and recruitment of stem cells in rats stops abdominal adhesions after laparotomy.\u0026quot; Scientific reports 9(1): 1-8\u003c/li\u003e\n\u003cli\u003eWang, D., et al. (2018). \u0026quot;The antifibrinolytic and anti‐inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial.\u0026quot; Journal of Thrombosis and Haemostasis 16(12): 2442-2453.\u003c/li\u003e\n\u003cli\u003eNg, W. C. K., et al. (2015). \u0026quot;Tranexamic acid: a clinical review.\u0026quot; Anaesthesiology intensive therapy 47(4): 339-350.\u003c/li\u003e\n\u003cli\u003eKer, K., et al. (2012). \u0026quot;Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis.\u0026quot; Bmj 344.\u003c/li\u003e\n\u003cli\u003eBose, T., et al. (2014). \u0026quot;Overview of nano-drugs characteristics for clinical application: the journey from the entry to the exit point.\u0026quot; Journal of nanoparticle research 16(8): 1-25.\u003c/li\u003e\n\u003cli\u003eNikolić, V., et al. (2019). Administration routes for nano drugs and characterization of nano drug loading. Characterization and biology of nanomaterials for drug delivery, Elsevier: 587-625.\u003c/li\u003e\n\u003cli\u003eLorenz, E., et al. (1997). Pathophysiology and classification of adhesions. Peritoneal adhesions, Springer: 29-34\u003c/li\u003e\n\u003cli\u003eParsaei, P., et al. (2013). \u0026quot;Bioactive components and preventive effect of green tea (Camellia sinensis) extract on post-laparotomy intra-abdominal adhesion in rats.\u0026quot; International Journal of Surgery 11(9): 811-815\u003c/li\u003e\n\u003cli\u003eAtarbashe, R. K. and A. Abu-Raghif (2020). \u0026quot;Comparative treatment of induced ulcerative colitis in male rat model by using cinnarizine and sulfasalazine.\u0026quot; Iraqi Journal of Veterinary Sciences 34(2): 465-472.\u003c/li\u003e\n\u003cli\u003eDiamond, M. P., et al. (2011). \u0026quot;A prospective, controlled, randomized, multicenter, exploratory pilot study evaluating the safety and potential trends in efficacy of Adhexil.\u0026quot; Fertility and sterility 95(3): 1086-1090.\u003c/li\u003e\n\u003cli\u003eSezer, U. A., et al. (2016). \u0026quot;Combination of gelatin and tranexamic acid offers improved haemostasis and safe use on internal hemorrhage control.\u0026quot; RSC advances 6(97): 95189-95198.\u003c/li\u003e\n\u003cli\u003eTopal E, Ozturk E, Şen G, Yerci O, Yılmazlar T. A Comparison of Three Fibrinolytic Agents in Prevention of Intra-Abdominal Adhesions. Acta Chir Belg [Internet]. 2010;110:71\u0026ndash;5. Available from: https://api.semanticscholar.org/CorpusID:23351061\u003c/li\u003e\n\u003cli\u003eSmith, J. A., et al. (2017). \u0026quot;Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.\u0026quot; \u003c/li\u003e\n\u003cli\u003eKoh A, Adiamah A, Sanyal S. 842 Safety and Efficacy of Tranexamic Acid to Minimise Perioperative Bleeding in Extrahepatic Abdominal Surgery: A Systematic Review. Br J Surg [Internet]. 2021;108. Available from: https://api.semanticscholar.org/CorpusID:236578483\u003c/li\u003e\n\u003cli\u003eWang D, Luo Z-Y, Yu Z-P, Liu L-X, Chen C, Meng W-K, et al. The antifibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial. J Thromb Haemost. 2018 Dec;16(12):2442\u0026ndash;53.\u003c/li\u003e\n\u003cli\u003eWiseman DM, Meidler R, Lyahovetsky Y, Kurman E, Horn S, Nur I. Evaluation of a fibrin preparation containing tranexamic acid (Adhexil) in a rabbit uterine horn model of adhesions with and without bleeding and in a model with two surgical loci. Fertil Steril. 2010 Mar;93(4):1045\u0026ndash;51.\u003c/li\u003e\n\u003cli\u003eWiseman DM, Lyachovetsky Y, Keidan I, Trout JR, Nur I. The effect of tranexamic acid in fibrin sealant on adhesion formation in the rat. J Biomed Mater Res B Appl Biomater [Internet]. 2004;68 2:222\u0026ndash;30. Available from: https://api.semanticscholar.org/CorpusID:37646051\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"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":"tranexamic acid, Nano particle, Abdominal adhesion, Laparotomy, Rat","lastPublishedDoi":"10.21203/rs.3.rs-5737190/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5737190/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e:Intra-abdominal adhesions frequently arise as a complication following abdominal surgeries. These adhesions lead to internal scarring as a result of damage to abdominal organs, including the peritoneum.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e:This research explores the effects of a Nano-formulated version of tranexamic acid on intra-abdominal adhesions in rats, utilizing both microscopic and macroscopic analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A total of thirty adult male Wistar rats (weighing between 300 and 350 grams) were randomly divided into three treatment groups: a control group, a group receiving Nano-drug tranexamic acid (50 mg/kg), and a group receiving standard tranexamic acid (50 mg/kg). Anesthesia was administered via intramuscular injections of 10% ketamine (50 mg/kg) and 2% xylazine (5 mg/kg) as per established guidelines. Adhesion was induced in all subjects by making incisions in the abdominal wall. On days 14 and 28 post-surgery, all rats underwent a second laparotomy, during which the extent of intra-abdominal adhesions was evaluated through both macroscopic and microscopic inspections.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e:The macroscopic evaluation indicated a marked reduction in the formation of adhesion bands within both the Nano-drug and standard drug treatment groups when compared to the control group (P\u0026lt;0.05). The Nano-drug treatment group exhibited the least amount of adhesion, whereas the control group showed the greatest incidence. Microscopic examination of pathological slides from the adhesion sites revealed that levels of inflammation and fibrotic tissue development were significantly reduced in both treatment groups versus the control group (P\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e:The Nano-drug group exhibited the lowest levels of inflammation and fibrotic tissue, while the highest levels were recorded in the control group.\u003c/p\u003e","manuscriptTitle":"Effect of nanoparticles of tranexamic acid on Intra-Abdominal Adhesion after Laparotomy on rat","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-02 08:59:51","doi":"10.21203/rs.3.rs-5737190/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":"fba6e325-a18f-4483-a96b-8693df61c7af","owner":[],"postedDate":"January 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-24T17:08:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-02 08:59:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5737190","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5737190","identity":"rs-5737190","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}