Effect of Tranexamic Acid Loaded Nanoparticles on Intra-Abdominal Adhesion Formation Following Laparotomy in Rats

Document Type : Original Article

Authors

1 Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman Iran

2 Department of Clinical Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran

Abstract

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. 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. 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. 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). The Nano-drug group exhibited the lowest levels of inflammation and fibrotic tissue, while the highest levels were recorded in the control group.

Keywords

Main Subjects


  1. Shahzamani S, Jahandideh A, Abedi G, Akbarzadeh A, Hesaraki S, Parsaei DP. Histopathological assessment of nano n-acetyl cysteine effect on postoperative adhesion in rats. Iraqi J Vet Sci. 2021;35:589-97. https://vetmedmosul.com/article_168409.html 
  2. Tabibian N, Swehli E, Boyd A, Umbreen A, Tabibian JH. Abdominal adhesions: a practical review of an often overlooked entity. Ann Med Surg. 2017;15:9-13. http://dx.doi.org/10.1016/j.amsu.2017.01.021 
  3. Ellis H, Moran BJ, Thompson JN, Parker MC, Wilson MS, Menzies D, et al. Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study. Lancet. 1999;353(9163):1476–80. https://doi.org/10.1016/S0140-6736(98)09337-4 
  4. Iwasaki K, Ahmadi AR, Qi L, Chen M, Wang W, Katsumata K, et al. Pharmacological mobilization and recruitment of stem cells in rats Stops Abdominal adhesions after laparotomy. Sci Rep. 2019;9(1):7149. https://doi.org/10.1038/s41598-019-43734-1 
  5. Wang D, Luo ZY, Yu ZP, Liu LX, Chen C, Meng WK, 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;16(12):2442-53. https://doi.org/10.1111/jth.14316 
  6. Ng W, Jerath A, Wąsowicz M. Tranexamic acid: a clinical review. Anaesthesiol Intensive Ther. 2015;47(4):339-50. https://doi.org/10.5603/ait.a2015.0011 
  7. Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ. 2012;344:e3054. https://doi.org/10.1136/bmj.e3054 
  8. Bose T, Latawiec D, Mondal P, Bullet M, Mandal S. Overview of nano-drugs characteristics for clinical application: the journey from the entry to the exit point. J Nanopart Res. 2014;16. https://doi.org/10.1007/s11051-014-2527-7
  9. Nikolić V, Ilic-Stojanovic S, Petrovic S, Tačić A, Nikolić L. Administration routes for nano drugs and characterization of nano drug loading. Characterization and biology of nanomaterials for drug delivery. 2019. p. 587-625. https://doi.org/10.1016/B978-0-12-814031-4.00021-0 
  10. Zühlke HV, Lorenz EM, Straub EM, Savvas V. Pathophysiology and classification of adhesions. Deutsche Gesellschaft für Chirurgie. Proceedings of the 1990 Congress. 1990. p. 1009-16. https://doi.org/10.1007/978-3-642-48163-5_212 
  11. Parsaei P, Karimi M, Asadi SY, Rafieian-Kopaei M. Bioactive components and preventive effect of green tea (Camellia sinensis) extract on post-laparotomy intra-abdominal adhesion in rats. Int J Surg. 2013;11(9):811-5. https://doi.org/10.1016/j.ijsu.2013.08.014 
  12. Atarbashe R, Abu Raghif A. Comparative treatment of induced ulcerative colitis in male rat model by using cinnarizine and sulfasalazine. Iraqi J Vet Sci. 2020;34:465-72. http://www.doi.org/10.33899/ijvs.2019.126170.1254 
  13. Diamond MP, Korell M, Martinez S, Kurman E, Kamar M. A prospective, controlled, randomized, multicenter, exploratory pilot study evaluating the safety and potential trends in efficacy of Adhexil. Fertil Steril. 2011;95(3):1086-90. https://doi.org/10.1016/j.fertnstert.2010.11.024 
  14. 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. 2010;110:71-5. https://api.semanticscholar.org/CorpusID:23351061 
  15. Koh A, Adiamah A, Sanyal S. Safety and efficacy of tranexamic acid to minimise perioperative bleeding in extrahepatic abdominal surgery: a systematic review. Br J Surg. 2021;108. https://doi.org/10.1093/bjsopen/zrab032.106 
  16. Sezer U, Kocer Z, Aru B, Demirel G, Gulmez M, Aktekin A, et al. Combination of gelatin and tranexamic acid offers improved haemostasis and safe use on internal hemorrhage control. RSC Adv. 2016;6:95189-98. https://doi.org/10.1039/C6RA16790J 
  17. Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, et al. Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med. 2017;376(2):136-48. https://doi.org/10.1056/nejmoa1606424 
  18. 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;93(4):1045-51. https://doi.org/10.1016/j.fertnstert.2008.11.026
  19. 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. 2004;68(2):222-30. https://doi.org/10.1002/jbm.b.20016