Abstract
Purpose: Gastric ischemia-reperfusion (IR) injury is a pathological event starting with tissue deoxygenation and then proceeding with the production of free oxygen radicals (FOR). For this reason, antioxidants are tested within the scope of gastric IR injury treatment. α-Lipoic acid (ALA) to be investigated in this study in terms of its protective effect against gastric IR injury is an endogenous antioxidant molecule synthesized from octanoic acid and cysteine in the cells. The aim of this study was to investigate the effect of ALA on IR induced gastric injury in male albino Wistar rats biochemically and histopathologically.
Materials and Methods: In the ALA+gastric ischemia-reperfusion group (AGIR) group, 100 mg/kg ALA was administered orally through a catheter. In the gastric ischemia-reperfusion group (GIR) and sham-operated group (SG), distilled water was administered as solvent. After 30 minutes of ALA and distilled water administration, all of the animals kept under anesthesia by intraperitoneal (ip) 25 mg/kg sodium thiopental sodium application and making the rats sniff xylazine at appropriate intervals. In order to induce IR lesions, the celiac artery of the animals in the AGIR and GIR groups was compressed with a clip to provide one hour of ischemia and three hours of reperfusion. The celiac artery of the SG group was closed with stitches without clipping. Then the rats were killed with a high dose (50 mg/kg) thiopental anesthesia. The biochemical and histopathological analyses were conducted on the gastric tissues removed from the killed rats.
Results: An increase for the amount of malondialdehyde (MDA), and a decrease in endogenous total antioxidant glutathione (tGSH) and superoxide dismutase (SOD) levels were found in the tissue of gastric treated with GIR. ALA prevented the increase in MDA and decrease in tGSH and SOD levels in gastric tissue caused by IR. In addition, ALA alleviated severe gastrointestinal hemorrhage, polymorpho nuclear leukocyte infiltration, edema, dilated congested blood vessels and destruction in the stomach caused by IR.
Conclusion: These findings indicate that ALA protects stomach against oxidative damage of IR. It has been suggested that ALA could beneficial in the treatment of gastric IR injury.
Keywords: Alpha-lipoic acid, gastric ischemia-reperfusion, protective impact.
References
- Yapca OE, Borekci B, Suleyman H. Ischemia-reperfusion damage. Eurasian J Med. 2013;45(2):126-7. doi: 10.5152/eajm.2013.24. Review
- Granger ND, Kvietys PR. Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol. 2015;6:524‐551
- Del Maestro RF. An approach to free radicals in medicine and biology. Acta physiologica Scandinavica. Supplementum. 1980; 492:153-168.
- Carden, D.L., Granger, D.N., pathophysiology of ischemia-reperfusion injury. J.Pathol. 2000; 190:255-66.
- Zimmerman BJ, Granger DN: Reperfusion injury. Surg Clin North Am. 1992; 72:65.
- Mythen, M.G. and A.R. Webb, Intraoperative Gut Mucosal Hypoperfusion Is Associated with Increased Postoperative Complications and Cost. Intensive Care Medicine. 1994; 20(2): 99-104
- Pena-Mercado E, Garcia-Lorenzana M, Arechaga E, la Rosa CH, Beltran NE.Gastric mucosa injury quantification in an ischemia – Reperfusion experimental model. Conf Proc IEEE Eng Med Biol Soc. 2016:2303-2306. doi: 10.1109/EMBC.2016.7591190.
- Golbidi S, Badran M, Laher I. Diabetes and alphalipoic Acid. Front Pharmacol. 2011; 2:69.
- Bilska A, Wlodek L. Lipoicacid – thedrug of thefuture? PharmacolRep 2005; 57: 570.
- Demiryilmaz, I., et al., Protective effect of nimesulide against hepatic ischemia/ reperfusion injury in rats: Effects on oxidant/antioxidants, DNA mutation and COX-1/COX-2 levels. Pharmacological Reports, 2014. 66(4): 647-652.
- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal Biochem.1979; 95 (2):315-8
- Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968; 25(1):192-205.
- Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988; 34(3):497-500.
- Brzozowski T, Konturek P. Role of gastric acid secretion in progression of acute erosions induced by ischemia-reperfusion into gastric ulcers. European Journal of Pharmacology, vol. 398, pp. 147-158, Jun. 2000.
- De La Lastra CA, Cabeza J, Motilva V, Martin MJ.Melatonin protects against gastric ischemia-reperfusion injury in rats.JPinealRes. 1997; 23(2):47-52.
- Hassan, H. Kashimura, K. Matsumaru, A. Nakahara, R. Iwata, T. Hayashi, H. Muto, N. Tanaka, K. Gotoand H. Fukutomi. Gastric mucosal injury induced by local ischemia-reperfusion in rats. Role of endogenous endothelin-1 and free radical. Digestive Diseases and science. 1997; 42:1375-1380.
- Mobarok Ali AM, Al-Rashed RS, Al-Swayeh OA, Al-Humayyd MS, Mustafa AA, Al Tuwaijiri AS. Selenium protects against ischemia-reperfusion¬ induced gastric lesions in rats .Saudi J Gastroenterol 1997; 3:125-9
- Goulart M, Batoreu MC, Rodrigues AS, Laires A, Rueff J. Lipoperoxidation products and thiol antioxidants in chromium exposed workers. Mutagenesis. 2005; 20: 311-315.
- Biewenga, G. P.,Haenen, G. R., &Bast, A. (1997). The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 29(3); 315-331.
- Biewenga, G. P.,Haenen, G. R., &Bast, A. (1997). The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 29(3); 315-331.
- El Eter E, Hagar HH, Al-Tuwaijiri A, Arafa M. Nuclear factor-kappa-B Inhibition by Pyrrolidinedithiocarbamate Attenuates Gastric Ischemia-Reperfusion Injury in Rats. Can J Physiol Pharmacol. 2005; 83:483-92.
- Çakır T, Baştürk A, Polat C, Aslaner A, Durgut H, Şehirli AÖ, Gül M, Öğünç AV, Gül S, Sabuncuoglu MZ, Oruç MT. Does alfa lipoic acid prevent liver from methotrexate induced oxidative injury in rats? Acta Cir Bras. 2015; 30(4):247-52.
- Buettner GR, Ng CF, Wang M, Rodgers VGJ, Schafer FQ. A new paradigm: Manganese superoxide dismutase influences the production of H2O2 in cells and thereby their biological state. Free Radical Biology and Medicine. 2006; 41:1338-1350.
- Magdy MA, Hanan el-A, Nabila el-M. Thymoquinone: Novel gastroprotective mechanisms. Eur J Pharmacol. 2012; 15:126-31.
- Çimen O, Çimen FK, Gülaboğlu M, Bilgin AÖ, Çekiç AB, Eken H, Süleyman Z, Bilgin Y, Altuner D. The effect of metyrosine on oxidative gastric damage induced by ischemia /reperfusion in rats. Biochemical and histopathological evaluation. Acta Cir Bras. 2018; 33:259-267.
- Liu Y, Gou L, Fu X, Li S, Lan N, Yin X. Protective effect of rutin against acute gastric mucosal lesions induced by ischemia - reperfusion. Pharm Biol. 2013; 51:914-9.
- Cui J, Liu L, Zou J, Qiao W, Liu H, Qi Y, Yan C. Protective effect of endogenous hydrogen sulfide against oxidative stress in gastric schemia - reperfusion injury. Exp Ther Med. 2013; 5(3):689-694.
- Hussein OA, Abdel-Hafez AMM, Abd El Kareim A. Rathippocampal CA3 neuronal injury induced by limb ischemia/ reperfusion: A possible restorative effect of alphalipoic acid. Ultrastruct Pathol. 2018; 42(2):133-154.
- Aydın A, Yıldırım AM. Effects of alphalipoicacid on ischemia-reperfusion injury in rat hind limb ischemia model. Ulus Travma Acil Cerrahi Derg. 2016; 22:509-515.
Corresponding Author
Orhan Cimen
Department of General Surgery, Faculty of Medicine, Erzincan University, Başbağlar Mah. 24100 Erzincan, Turkey
DOI: https://dx.doi.org/10.18535/jmscr/v8i6.100
