Protection against dextran sodium sulfate-induced colitis by dehydroepiandrosterone and 7α-hydroxy-dehydroepiandrosterone in the rat

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• 作者：Marie-Agnè ; s Pé ; lissier ; Caroline Muller ; Martin Hill and Robert Morfin
• 关键词：DHEA ; 7α ; -Hydroxy-DHEA ; 11β ; -HSD ; Oxidative stress ; Goblet cells
• 刊名：Steroids
• 出版年：2006
• 期刊代码：142_0039128x
• 类别：bio
• 出版时间：March 2006
• 卷：71
• 期：3
• 页码：240-248
• 文件大小：277 K

摘要

In this study the anti-oxidant effect of DHEA and 7α-hydroxy-DHEA against oxidative stress induced by colitis was investigated in vivo in rats. The two steroids were intraperitoneally injected once daily (50 mg/kg body weight) for 7 days before the induction of colitis that was effected by a daily treatment of 5%(w/v) dextran sodium sulfate (DSS) in drinking water for 7 days. This was quantified by the evidence of weight loss, rectal bleeding, increased wall thickness, and colon length. The inflammatory response was assessed by neutrophil infiltration after a histological examination and myeloperoxidase (MPO) activity measurement. Two markers of oxidative damage were measured in colon homogenates after the onset of DSS treatment: protein carbonyls and thiobarbituric acid-reacting substances. The colonic metabolism of corticosterone by 11β-hydroxysteroid dehydrogenases types 1 and 2 (11β-HSD) was investigated in control and treated animals.

Results indicated that colitis caused a decrease in body weight and colon length. Severe lesions were observed in the colon with a reduced number of goblet cells which contained less mucins. The lesions were associated with increased MPO activity and oxidative damage. Colonic inflammation down and up regulated the 11β-HSD2 and 11β-HSD1, respectively. Treatments by DHEA and 7α-hydroxy-DHEA attenuated the inflammatory response when MPO activity decreased; but this did not increase the colonic oxidation of corticosterone into 11-dehydrocorticosterone. Both DHEA and 7α-hydroxy-DHEA exerted a significant anti-oxidant effect against oxidative stress induced by colitis through reducing the oxidative damage to proteins and lipids. This resulted in a moderate increase in the amount of colonic mucus. Both DHEA and 7α-hydroxy-DHEA may prove useful in the prevention or treatment of colitis.