Taye Ashraf, Saad Adel H
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Egypt.
Department of physiology, Faculty of Medicine, Minia University, Egypt.
Gastroenterology Res. 2009 Dec;2(6):324-332. doi: 10.4021/gr2009.12.1328. Epub 2009 Nov 20.
Rosiglitazone, an insulin sensitizing agent, has been recently implicated in the control of inflammatory processes and modulation of expression of various cytokines such as tumor necrosis factor (TNF-α). However, its mechanistic effect of gastric mucosal integrity remains to be elucidated.
The present study was designed to determine effect of rosiglitazone on gastric mucosal lesions induced by indomethacin (IND) in rats. Pyloric ligation was performed for the collection of gastric juice, and gastric ulceration was induced by a single intraperitoneal injection of IND (30 mg/kg).
IND administration caused a significant decrease in the volume of gastric juice mucin and gastric mucosal nitrite and prostaglandin E (PGE) levels. This was accompanied by a significant increase in gastric juice free and total acidity and pepsin activity. In addition, an elevation in the gastric mucosal lipid peroxide and serum TNF-α level was observed. Pretreatment with rosiglitazone (10 mg/kg, orally, for 1 weeks) resulted in a significant reduction in the elevated gastric mucosal lesions and lipid peroxides levels. This was associated with a marked increase in gastric juice mucin and a reduction in TNF-α level. Moreover, rosiglitazone significantly increased the gastric mucosal total nitrite and PGE levels.
Rosiglitazone exerts a gastroprotective effect against IND-induced gastric mucosal lesions and its anti-ulcer effect is mediated via scavenging free radicals, increasing NO, PGE and mucus production in addition to its anti-inflammatory mechanisms. Thus, rosiglitazone could be a relevant drug for patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and at high risk of developing gastric ulceration.
罗格列酮是一种胰岛素增敏剂，最近被认为与炎症过程的控制以及多种细胞因子如肿瘤坏死因子（TNF-α）表达的调节有关。然而，其对胃黏膜完整性的作用机制仍有待阐明。
本研究旨在确定罗格列酮对吲哚美辛（IND）诱导的大鼠胃黏膜损伤的影响。进行幽门结扎以收集胃液，通过单次腹腔注射IND（30mg/kg）诱导胃溃疡。
给予IND导致胃液黏液、胃黏膜亚硝酸盐和前列腺素E（PGE）水平显著降低。同时，胃液游离酸和总酸度以及胃蛋白酶活性显著增加。此外，观察到胃黏膜脂质过氧化物和血清TNF-α水平升高。罗格列酮预处理（10mg/kg，口服，共1周）导致胃黏膜损伤和脂质过氧化物水平的显著降低。这与胃液黏液的显著增加和TNF-α水平的降低相关。此外，罗格列酮显著增加了胃黏膜总亚硝酸盐和PGE水平。
罗格列酮对IND诱导的胃黏膜损伤具有胃保护作用，其抗溃疡作用是通过清除自由基、增加一氧化氮、PGE和黏液分泌以及其抗炎机制介导的。因此，罗格列酮可能是服用非甾体抗炎药（NSAIDs）且发生胃溃疡风险较高的患者的一种相关药物。
