The effect of Ginkgo biloba EGb 761 on intestinal anastomotic healing in rats with ischemia-reperfusion induced in the lower extremities

Year 2021, Volume: 5 Issue: 12, 1164 - 1169, 01.12.2021

Serdar Basim Pelin Basim , Okan Demiray

https://doi.org/10.28982/josam.890700

Abstract

Background/Aim: Remote ischemia-reperfusion (I-R) injury for anastomotic healing is a newly identified risk factor and there is a wide array of studies being conducted. This study aimed to reveal the negative effects of lower I-R on the colonic anastomotic healing process and examine the effects of Ginkgo biloba EGb 761 treatment, a platelet activating factor (PAF) antagonist, on anastomotic healing through the inhibition of pathological mechanisms of mediators causing these negative effects.
Methods: Thirty-six Wistar-Albino rats were divided into sham, I-R and I-R+EGb 761 groups, each consisting of 12 rats. In the subjects in the sham group, an end-to-end anastomosis was performed by transecting the descending colon following midline laparotomy. In the I-R group, unilateral lower extremity ischemia was created by occluding the femoral artery and collaterals using a tourniquet from the most proximal segment of the left extremity. Then, the descending colon was transected, anastomosis was performed, and reperfusion was created by a tourniquet application at the 30th minute of ischemia. Different from the I-R (control) group, the subjects in the I-R+EGb 761 group were given two equal doses of 64 mg/kg/d Ginkgo biloba EGb 761 by the orogastric route until 10 days after surgery. After all subjects were sacrificed on the 10th day of surgery, the descending colon segment containing the anastomosis area was resected and samples were taken for bursting pressure and hydroxyproline measurements.
Results: In the I-R group, anastomotic bursting pressure and perianastomotic hydroxyproline values were significantly lower compared to the sham group and the I-R+EGb 761 group. However, there was no statistically significant difference in these parameters between the sham and the I-R+EGb 761 groups.
Conclusion: Colonic anastomotic bursting pressure and peri-anastomotic hydroxyproline values in the sham group were significantly decreased by lower extremity I-R, and this change was prevented with the use of EGb 761.

Keywords

Remote ischemia-reperfusion, Ginkgo biloba EGb 761, PAF Antagonist

References

• 1. Dietz UA, Debus E-S. Intestinal anastomoses prior to 1882; a legacy of ingenuity, persistence, and research form a foundation for modern gastrointestinal surgery. World J Surg. 2005;29:396-401.
• 2. Kuzu MA, Köksoy C, Kale IT, Tanik A, Terzi C, Elhan AH. Reperfusion injury delays healing of intestinal anastomosis in a rat. Am J Surg. 1998;176:348-51.
• 3. Grace PA. Ischaemia-reperfusion injury. Br J Surg. 1994;81:637-47.
• 4. Kartal H, Büyük B. Effects of alpha-lipoic acid on skeletal muscle ischemia-reperfusion injury in mice. J Surg Med. 2020; 4(7): 567-572.
• 5. Zimmerman BJ, Granger DN. Reperfusion injury. Surg Clin North Am. 1992;72:65-83.
• 6. Souza DG, Cara DC, Cassali GD, Coutinho SF, Silveira MR, Andrade SP, et al. Effects of the PAF receptor antagonist UK74505 on local and remote reperfusion injuries following ischaemia of the superior mesenteric artery in the rat. Br J Pharmacol. 2000;131:1800-8.
• 7. Carter MB, Wilson MA, Wead WB, Garrison RN. Platelet-activating factor mediates pulmonary macromolecular leak following intestinal ischemia-reperfusion. J Surg Res. 1996;60:403-8.
• 8. Börjesson A, Wang X, Sun Z, Inghammar M, Truedsson L, Andersson R. Early treatment with lexipafant, a platelet-activating factor-receptor antagonist, is not sufficient to prevent pulmonary endothelial damage after intestinal ischaemia and reperfusion in rats. Dig Liver Dis. 2002;34:190-6.
• 9. Sun Z, Wang X, Deng X, Lasson A, Soltesz V, Börjesson A, et al. Beneficial effects of lexipafant, a PAF antagonist on gut barrier dysfunction caused by intestinal ischemia and reperfusion in rats. Dig Surg. 2000;17:57-65.
• 10. Pehlivan M, Dalbeler Y, Hazinedaroglu S, Arikan Y, Erkek AB, Günal O, et al. An assessment of the effect of Ginkgo Biloba EGb 761 on ischemia reperfusion injury of intestine. Hepatogastroenterology. 2002;49:201-4.
• 11. Noel AA, Hobson RW 2nd, Durán WN. Platelet-activating factor and nitric oxide mediate microvascular permeability in ischemia-reperfusion injury. Microvasc Res. 1996;52:210-20.
• 12. Louajri A, Harraga S, Godot V, Toubin G, Kantelip JP, Magnin P. The effect of ginkgo biloba extract on free radical production in hypoxic rats. Biol Pharm Bull. 2001;24:710-2.
• 13. Schutte A, Topp SA, Knoefel WT, Brilloff S, Mueller L, Rogiers X, et al. Influence of Ginkgo Biloba extract (EGB 761) on expression of EGR-1 mRNA and HSP-70 mRNA after warm ischemia in the rat liver. Transplant Proc. 2001;33:3724-5.
• 14. Christen Y, Maixent JM. What is Ginkgo biloba extract EGb 761? An overview--from molecular biology to clinical medicine. Cell Mol Biol (Noisy-le-grand). 2002;48:601-11.
• 15. Kecskeméti V, Balogh I. The role of platelet-activating factor (PAF) antagonists and nitric oxide in cardiac actions of PAF. Electrophysiological and morphological study. J Physiol Pharmacol. 2000;51:723-35.
• 16. Kohlman-Trigoboff D, Gongora E, Stanford J, Smith BM. Risk factors associated with acute lower extremity ischemia after coronary revascularization. J Vasc Nurs. 2002;20:78-83.
• 17. Wehrens XH, Rouwet EV, oude Egbrink MG, Slaaf DW, Ramsay G. Effects of experimental lower-limb ischaemia-reperfusion injury on the mesenteric microcirculation. Br J Surg. 2002;89:185-91.
• 18. Ateş M, Köksal MH, Celayir MF, Baykan A. Prophylactic and therapeutic effect of ginko biloba extract (Egb761) on mortality of intestinal deep ischemia-reperfusion model in rats. Dicle Medical Journal. 2010;37:199-203.
• 19. Parks DA, Granger DN. Contributions of ischemia and reperfusion to mucosal lesion formation. Am J Physiol. 1986;250:G749-53.
• 20. Kologlu M, Yorganci K, Renda N, Sayek I. Effect of local and remote ischemia-reperfusion injury on healing of colonic anastomoses. Surgery. 2000;128:99-104.
• 21. Mansour Z, Charles AL, Kindo M, Pottecher J, Chamaraux-Tran TN, Lejay A, et al. Remote effects of lower limb ischemia-reperfusion: impaired lung, unchanged liver, and stimulated kidney oxidative capacities. Biomed Res Int. 2014;2014:392390.
• 22. Yassin MM, Barros D'Sa AA, Parks G, Abdulkadir AS, Halliday I, Rowlands BJ. Mortality following lower limb ischemia-reperfusion: a systemic inflammatory response? World J Surg. 1996;20:961-7.
• 23. Stammberger U, Carboni GL, Hillinger S, Schneiter D, Weder W, Schmid RA. Combined treatment with endothelin- and PAF-antagonists reduces posttransplant lung ischemia/reperfusion injury. J Heart Lung Transplant. 1999;18:862-8.
• 24. Tekin K, Aytekin F, Ozden A, Bilgihan A, Erdem E, Sungurtekin U, et al. Antithrombin III prevents deleterious effects of remote ischemia-reperfusion injury on healing of colonic anastomoses. Am J Surg. 2002;184:160-5.
• 25. Kologlu M, Sayek I, Kologlu LB, Onat D. Effect of persistently elevated intraabdominal pressure on healing of colonic anastomoses. Am J Surg. 1999;178:293-7.
• 26. Tang Y, Zhou G, Yao L, Xue P, Yu D, Xu R, et al. Protective effect of Ginkgo biloba leaves extract, EGb761, on myocardium injury in ischemia reperfusion rats via regulation of TLR-4/NF-κB signaling pathway. Oncotarget. 2017;8:86671-80.