Protective Effects of Diallyl Sulfide against Thioacetamide-Induced Toxicity: A Possible Role of Cytochrome P450 2E1

Title
Protective Effects of Diallyl Sulfide against Thioacetamide-Induced Toxicity: A Possible Role of Cytochrome P450 2E1
Author(s)
정태천김남희[김남희]이상규[이상규]강미정정혜광[정혜광]강원구[강원구]
Keywords
ORGANOSULFUR COMPOUNDS; INDUCED HEPATOTOXICITY; SKIN CARCINOGENESIS; ANTITUMOR-ACTIVITY; S-OXIDE; METABOLISM; RAT; MICE; IMMUNOSUPPRESSION; ENZYMES
Issue Date
201403
Publisher
KOREAN SOC APPLIED PHARMACOLOGY
Citation
BIOMOLECULES & THERAPEUTICS, v.22, no.2, pp.149 - 154
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.
URI
http://hdl.handle.net/YU.REPOSITORY/32862http://dx.doi.org/10.4062/biomolther.2014.016
ISSN
1976-9148
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약학대학 > 약학부 > Articles
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