Evaluation of hepatotoxicity and oxidative stress in rats treated with tert-butyl hydroperoxide

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• 作者：Jung Min Oh^a ; ¹ ; Young Suk Jung^b ; ¹ ; Byung Suk Jeon^c ; Byung Il Yoon^c ; Kye Sook Lee^a ; ^d ; Bong Hee Kim^a ; Soo Jin Oh^d ; ^{diatree@kribb.re.kr} ; Sang Kyum Kim^a ; ^{sangkim@cnu.ac.kr}
• 关键词：t-BHP ; Oxidative stress ; Hepatotoxicity ; Antioxidant activity ; GSH
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：May, 2012
• 卷：50
• 期：5
• 页码：1215-1221
• 文件大小：910 K

摘要

Although tert-butyl hydroperoxide (t-BHP) is commonly used to induce oxidative stress, little is known about the time- or dose-dependence of its oxidative effects. In this study, we examined hepatotoxicity and oxidative stress in male rats at various times (0-24 h) after t-BHP (0, 0.2, 0.5, 1 or 3 mmol/kg, ip) treatment. Serum hepatotoxicity parameters were increased from 2 h following 1 mmol/kg t-BHP and reached their maximum values at 8 h. Plasma malondialdehyde levels were maximally elevated by 62%at 0.5 h and returned to control levels by 4 h. Hepatic glutathione levels were decreased between 0.5 and 2 h, and hepatic glutathione disulfide levels were increased at 2 h. Interestingly, hepatic glutathione levels were increased at 24 h, which may be attributed to up-regulation of glutathione synthesis through induction of gamma-glutamylcysteine ligase expression. The elevation of hepatotoxic parameters and plasma MDA was observed from 0.5 to 1 mmol/kg t-BHP, respectively, in a dose-dependent manner. Considering that the maximal dose resulted in 20%lethality, 1 mmol/kg of t-BHP may be suitable for evaluating antioxidant activity of tested compounds. Our results provide essential information to characterize the t-BHP-induced oxidative stress and hepatotoxicity.