title: Enhanced hepatotoxicity induced by repeated exposure to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin in combination in male rats.
abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are among persistent polyhalogenated aromatic hydrocarbons that exist as complex mixtures in the environment worldwide. The present study was attempted to investigate the hepatotoxicity following repeated exposure to TCDD and PCBs in combination in male rats, and to reveal the involvement of potential mechanisms. Male Sprague-Dawley rats were exposed to TCDD (10 microg/kg) and Aroclor 1254 (10 mg/kg, a representative mixture of PCBs) alone or in combination by intragastric administration. After 12-day exposure, all treatments produced significant hepatotoxicity as characterized by changes of plasma biochemistry and histopathological changes. These effects were more prominent in the combined group. Furthermore, all treatments induced hepatic cytochrome P450 1A1 (CYP1A1) expression, and the maximal level of CYP1A1 expression was observed in the combined group, as in the case of the most severe hepatotoxicity evoked by the combined exposure. These findings indicated that the hepatotoxicity induced by TCDD and Aroclor 1254 might be ascribed to the high expression of hepatic CYP1A1. The present study demonstrates the enhanced hepatotoxicity after exposure to TCDD and PCBs in combination in rats.
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China. wangyimei2006@126.com
authors.forename: Yimei
authors.initials: Y
authors.lastname: Wang
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Lu
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Sheng
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Ze
authors.initials: Z
authors.lastname: Fu
authors.forename: Benzhan
authors.initials: B
authors.lastname: Zhu
authors.forename: Shuangqing
authors.initials: S
authors.lastname: Peng
mesh_terms: D000818:Animals; D020111:Chlorodiphenyl (54% Chlorine) / Q000008:administration & dosage* / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D020111:Chlorodiphenyl (54% Chlorine); D019363:Cytochrome P-450 CYP1A1