Protective Effects of Diallyl Sulfide against Thioacetamide-Induced Toxicity: A Possible Role of Cytochrome P450 2E1.
- Author:
Nam Hee KIM
1
;
Sangkyu LEE
;
Mi Jeong KANG
;
Hye Gwang JEONG
;
Wonku KANG
;
Tae Cheon JEONG
Author Information
1. College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. taecheon@ynu.ac.kr
- Publication Type:Original Article
- Keywords:
Diallyl sulfide;
Thioacetamide;
CYP;
Toxicity;
Metabolic activation
- MeSH:
Alanine Transaminase;
Animals;
Antibody Formation;
Aspartate Aminotransferases;
Biotransformation;
Blotting, Western;
Corn Oil;
Cytochrome P-450 CYP2E1*;
Cytochrome P-450 Enzyme System;
Erythrocytes;
Female;
Humans;
Male;
Mice;
Rats;
Rats, Sprague-Dawley;
Sheep;
Thioacetamide
- From:Biomolecules & Therapeutics
2014;22(2):149-154
- CountryRepublic of Korea
- Language:English
-
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.
