Iran J Vet Surg, Print ISSN: 2008-3033, Online ISSN: 2676-6299

Document Type : Original Article

Authors

1 Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

Abstract

Objective- Leakage after colon anastomosis is the most common complication with the highest mortality rate. Silymarin possesses potent anti-inflammatory, antioxidant, reparative and antibacterial activities and therefore has been used to accelerate different experimental wound healing models. This study was aimed to investigate effects of orally administered silymarin following colonic resection and anastomosis in terms of histopathological and mechanical parameters.
Design- An experimental study.
Animals- Twenty four male mature Wistar rats
Procedures- The rats were divided randomly into two groups. After aseptic preparation, descending colon was exteriorized thorough laparotomy. Then, colon resection and end to end anastomosis was performed in all rats. The control rats were gavaged with 1 ml normal saline post operatively as placebo while the rats in the treatment group received 50 mg/kg silymarin suspended in 1 ml normal saline for five consecutive days. At the 7th day, all rat were euthanized.
Results- Necropsy finding showed that leakage, adhesion formation and peritonitis scores in treatment group were significantly decreased. On histopathology, decreased inflammatory cell infiltration was observed in the treatment group. While, the scores of angiogenesis, cell proliferation, and collagen deposition were significantly increased in the treatment group. No significant difference was observed in bursting pressure when control samples were compared to the silymarin treated ones. Furthermore, mechanical properties (including: maximum load, yield load, and absorbed energy) in treatment group were significantly increased compared to control group.
Conclusion and Clinical Relevance- The results of the present study showed that oral administration of silymarin following colonic anastomosis in rats improves the structural indices of wound healing and its mechanical characteristics with lower rates of anastomotic complications.

Keywords

Main Subjects

  1. Clifford RE, Fowler H, Govindarajah N, Vimalachandran D, Sutton PA. ‎Early anastomotic complications in colorectal surgery: a systematic review of ‎techniques for endoscopic salvage. Surgical Endoscopy, 2019; 33(4):1049-1065. ‎
  2. ‎Radlinsky MG, Fossum TW. Surgery of the digestive system. In: Fossum TW‎. Small animal surgery. Philadelphia: Elsevier; 2019: 331-511.‎
  3. ‎Ho YH, Ashour MA. Techniques for colorectal anastomosis. World Journal of Gastroenterology, 2010; 16(13): 1610-1621.
  4. ‎‎Ikada Y. Challenges in tissue engineering. Journal of the Royal Society Interface, 2006; 3(10): 589-601.
  5. ‎Drmic D, Kolenc D, Ilic S, Bauk L, Sever M, Zenko Sever A, Luetic K, Suran J, Seiwerth S, Sikiric P. Celecoxib-induced gastrointestinal, liver and ‎brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by ‎L-NAME. World Journal of Gastroenterology, 2017; 23(29): 5304-5312.
  6. ‎Lin D, Chen K, Xie M, Ye L, Chan EW, Chen S. Effect of ceftiofur and ‎enrofloxacin on E. coli sub-population in pig gastrointestinal tract. Journal of Global Antimicrobial Resistance, 2017; 10: 126-130.‎
  7. ‎‎Ashkani-Esfahani S, Emami Y, Esmaeilzadeh E, Bagheri F, Namazi MR, ‎Keshtkar M, Khoshneviszadehd M, Noorafshane A. Silymarin enhanced fibroblast proliferation and tissue ‎regeneration in full thickness skin wounds in rat models; a stereological study. Journal of the Saudi Society of Dermatology & Dermatologic Surgery, 2013; 17(1): 7-12.
  8. ‎Katiyar SK. Silymarin and skin cancer prevention: anti-inflammatory, ‎antioxidant and immunomodulatory effects (Review). International Journal of Oncology, 2005; 26(1): ‎‎169-176.‎
  9. ‎Esmaily H, Hosseini-Tabatabaei A, Rahimian R. Khorasani R, Baeeri M, ‎Barazesh Morgani AR, Yasa N, Khademi Y, Abdollahi M. On the benefits of silymarin in murine colitis by ‎improving balance of destructive cytokines and reduction of toxic stress in the ‎bowel cells. Central European Journal of Biology, 2009; 4: 204.
  10. ‎Cruz T, Gálvez J, Crespo E, Ocete MA, Zarzuelo A. Effects of silymarin on the acute stage of the trinitrobenzenesulphonic acid model of rat colitis. Planta Medica, 2001; 67(1): 94-96. ‎
  11. Rastegarpanah M, Malekzadeh R, Vahedi H, Mohammadi M, Elahi E, ‎Chaharmahali M, Safarnavadeh T, Abdollahi M. A randomized, double ‎blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis. Chinese Journal of Integrative Medicine, 2015; 21(12) :902-906.
  12. Kisli E, Ozdemir H, Kösem M, Sürer H, Ciftçi A, Kanter M. Effect of Ginkgo biloba extract (EGb 761) on the healing of left colonic anastomoses in rat. World Journal of Surgery, 2007; 31(8): 1652-1657.
  13. ‎Despoudi K, Mantzoros I, Ioannidis O, Cheva A, Antoniou N, Konstantaras D, Symeonidis S, Pramateftakis MG, Kotidis E, Angelopoulos S, Tsalis K. Effects of ‎albumin/glutaraldehyde glue on healing of colonic anastomosis in rats. ‎ Gastroenterology, 2017; 23(31): 5680-5691.
  14. ‎Wu Z, Daams F, Boersema GS, Vakalopoulos KA, Lam KH, van der Horst PH, Kleinrensink GJ, Jeekel J, Lange JF. Colorectal anastomotic leakage caused by insufficient suturing ‎after partial colectomy: a new experimental model. Surgical Infections (Larchmt), ‎‎2014; 15: 733-738.‎
  15. ‎Lorenzi T, Trombettoni MMC, Ghiselli R, Paolinelli F, Gesuita R, Cirioni O, Provinciali M, Kamysz W, Kamysz E, Piangatelli C, Castellucci M, Guerrieri M, Morroni M. Effect of omiganan on colonic anastomosis healing in a rat ‎model of peritonitis. American Journal of Translational Research, 2017; 9(7): 3374-3386. ‎
  16. ‎Tallón-Aguilar L, Lopez-Bernal Fde A, Muntane-Relat J, García-‎Martínez JA, Castillo-Sanchez E, Padillo-Ruiz J. The use of TachoSil as sealant ‎in an experimental model of colonic perforation. Surgical Innovation, 2015; 22(1): 54-60. ‎
  17. ‎Thomas MS, Margolin DA. Management of colorectal anastomotic ‎leak. Clinics in Colon and Rectal Surgery, 2016; 29(2): 138-144.‎
  18. Takhshid M, Rosta A, Tavasouli A, Khabaz Z. Protective effects of silymarin on acetic acid –induced colitis in rats. Journal of Mazandaran University of Medical Sciences, 2011; 21(84): 53-61.
  19. ‎Toutouzas K, Kleidi ES, Drimousis PG, Balla M, Papanikolaou MN, Larentzakis A, Theodorou D, Katsaragakis S. Anastomotic leak management after a low anterior ‎resection leading to recurrent abdominal compartment syndrome: a case report ‎and review of the literature. Journal of Medical Case Reports, 2009; 3: 125.‎
  20. ‎Gutmann J, Penzias AS, Diamond MP. Adhesions in reproductive ‎surgery. In: Wallach EE, Zacur HA. Reproductive medicine and surgery, St. Louis, USA: Mosby; 1995: 681-693.‎
  21. ‎Karimi M, Parsaei P, Shafiei-Alavijeh S, Rafieian-Kopaei M, Asadi SY. ‎Effect of silymarin alcoholic extract on surgery-induced intraperitoneal ‎adhesion in rats. Surgical Practice, 2016; 20(1): 27-33.‎
  22. ‎Tabandeh MR, Oryan A, Mohhammad-Alipour A, nd Tabatabaei-Naieni A. ‎Silibinin regulates matrix metalloproteinase 3 (stromelysine1) gene expression, ‎hexoseamines and collagen production during rat skin wound healing. Phytotherapy Research, 2013; 27: 1149-1153.‎
  23. ‎Stumpf M, Cao W, Klinge U, Klosterhalfen B, Kasperk R, Schumpelick ‎V. Collagen distribution and expression of matrix metalloproteinases 1 and 13 ‎in patients with anastomotic leakage after large-bowel surgery. Langenbeck's Archives of Surgery, 2002; 386(7): 502-506.
  24. ‎Munireddy S, Kavalukas SL, Barbul A. Intra-abdominal healing: ‎gastrointestinal tract and adhesions. Surgical Clinics of North America, 2010; 90(6): 1227-1236.‎
  25. ‎Mastboom WJ, Hendriks T, van Elteren P, de Boer HH. The influence of ‎NSAIDs on experimental intestinal anastomoses. Diseases of the Colon & Rectum, ‎‎1991; 34(3): 236-243.
  26. ‎Davies NM. Toxicity of nonsteroidal anti-inflammatory drugs in the ‎large intestine. Diseases of the Colon & Rectum, 1995; 38(12): 1311-1321.‎
  27. ‎‎Holt DE, Brockman D. Large intestine. In: Slatter DH. Textbook of ‎small animal surgery. 3rd ed. Philadelphia, USA: Saunders; 2003: 665-682.‎
  28. ‎Hendriks T, Mastboom WJ. Healing of experimental intestinal ‎anastomoses. Parameters for repair. Diseases of the Colon & Rectum, 1990; 33: 891-901.‎
  29. ‎Månsson P, Zhang XW, Jeppsson B, Thorlacius H. Anastomotic healing ‎in the rat colon: comparison between a radiological method, breaking strength ‎and bursting pressure. International Journal of Colorectal Disease, 2002; 17(6): 420-425. ‎
  30. ‎Ikeuchi D, Onodera H, Aung T, Kan S, Kawamoto K, Imamura M, Maetani S. ‎Correlation of tensile strength with bursting pressure in the evaluation of ‎intestinal anastomosis. Digestive Surgery, 1999; 16: 478-485.‎
  31. ‎Oryan A, Tabatabaei Naeini A, Moshiri A, Mohammadalipour A, ‎Tabandeh MR. Modulation of cutaneous wound healing by silymarin in rats. Journal of Wound Care, 2012; 21 (9): 457-464.‎
  32. ‎‎‎Haugh MG, Jaasma MJ, O'Brien FJ. The effect of dehydrothermal ‎treatment on the mechanical and structural properties of collagen-GAG ‎scaffolds. Journal of Biomedical Materials Research, 2009; 89(2): 363-369.