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半胱氨酸前药及抗氧化剂L-2-氧代噻唑烷-4-羧酸对大鼠乙醇诱导的胃损伤的保护作用

Protective effect of a cysteine prodrug and antioxidant, L-2-oxothiazolidine-4-carboxylate, against ethanol-induced gastric lesions in rats.

作者信息

Al Moutaery Meshal, Al Rayes Hannan, Al Swailam Ramaiz, Elfaki Ibrahim, Khan Haseeb Ahmad, Arshaduddin Mohammad, Tariq Mohammad

机构信息

Prince Sultan Cardiac Center, Armed Forces Hospital, Riyadh, Saudi Arabia.

出版信息

Exp Toxicol Pathol. 2012 Mar;64(3):233-7. doi: 10.1016/j.etp.2010.08.012. Epub 2010 Sep 9.

DOI:10.1016/j.etp.2010.08.012
PMID:20829008
Abstract

Earlier studies have suggested an important role of glutathione (GSH) in cytoprotection against free radicals induced oxidative damage. This study reports gastroprotective effects of a cysteine precursor, L-2-oxothiazolidine-4-carboxylate (OTC), in experimental models of gastric secretion and ulceration. Acid secretion studies (volume and acidity) were undertaken in pylorus-ligated rats whereas the gastric lesions were induced by ethanol. Different groups of animals were treated with OTC (0, 100, 200 and 400 mg/kg). The levels of gastric wall mucus, nonprotein sulfhydryls (NP-SH) and myeloperoxidase (MPO) were measured in the glandular stomach of rats following ethanol-induced gastric lesions. Both medium and high doses of OTC significantly reduced the volume and acidity of gastric secretion in pylorus-ligated rats. Pretreatment with OTC significantly and dose-dependently attenuated the formation of ethanol-induced gastric lesion. OTC significantly protected the gastric mucosa against ethanol-induced depletion of gastric wall mucus, NP-SH and MPO. The gastroprotective effects of OTC may be attributed to its ability to inhibit neutrophils activity and replenish GSH demand.

摘要

早期研究表明,谷胱甘肽(GSH)在细胞保护免受自由基诱导的氧化损伤中发挥重要作用。本研究报告了半胱氨酸前体L-2-氧代噻唑烷-4-羧酸(OTC)在胃分泌和溃疡实验模型中的胃保护作用。在幽门结扎大鼠中进行酸分泌研究(体积和酸度),而乙醇诱导胃损伤。不同组动物用OTC(0、100、200和400mg/kg)治疗。在乙醇诱导胃损伤后,测定大鼠腺胃中胃壁黏液、非蛋白巯基(NP-SH)和髓过氧化物酶(MPO)水平。中、高剂量OTC均显著降低幽门结扎大鼠胃分泌的体积和酸度。OTC预处理显著且剂量依赖性地减轻乙醇诱导的胃损伤形成。OTC显著保护胃黏膜免受乙醇诱导的胃壁黏液、NP-SH和MPO消耗。OTC的胃保护作用可能归因于其抑制中性粒细胞活性和补充GSH需求的能力。

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