title: Protective Effects of Diallyl Sulfide against Thioacetamide-Induced Toxicity: A Possible Role of Cytochrome P450 2E1.
abstract: Effects of diallyl sulfide (DAS) on thioacetamide-induced hepatotoxicity and immunotoxicity were investigated. When male Sprague-Dawley rats were treated orally with 100, 200 and 400 mg/kg of DAS in corn oil for three consecutive days, the activity of cytochrome P450 (CYP) 2E1-selective p-nitrophenol hydroxylase was dose-dependently suppressed. In addition, the activities of CYP 2B-selective benzyloxyresorufin O-debenzylase and pentoxyresorufin O-depentylase were significantly induced by the treatment with DAS. Western immunoblotting analyses also indicated the suppression of CYP 2E1 protein and/or the induction of CYP 2B protein by DAS. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 400 mg/kg of DAS for 3 days, followed by a single intraperitoneal treatment with 100 and 200 mg/kg of thioacetamide in saline for 24 hr. The activities of serum alanine aminotransferase and aspartate aminotransferase significantly elevated by thioacetamide were protected in DAS-pretreated animals. Likewise, the suppressed antibody response to sheep erythrocytes by thioacetamide was protected by DAS pretreatment in female BALB/c mice. Taken together, our present results indicated that thioacetamide might be activated to its toxic metabolite(s) by CYP 2E1, not by CYP 2B, in rats and mice.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Wonku
authors.initials: W
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
keywords: CYP; Diallyl sulfide; Metabolic activation; Thioacetamide; Toxicity
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