Evaluation of hepatotoxicity and oxidative stress in rats treated with tert-butyl hydroperoxide.
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 2h. 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.
College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
Jung Min
JM
Oh
Young Suk
YS
Jung
Byung Suk
BS
Jeon
Byung Il
BI
Yoon
Kye Sook
KS
Lee
Bong Hee
BH
Kim
Soo Jin
SJ
Oh
Sang Kyum
SK
Kim
D000818:Animals; D008099:Liver / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
D020122:tert-Butylhydroperoxide