Enhanced hepatotoxicity induced by repeated exposure to polychlorinatedbiphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin in combination in male rats
Yimei Wang , Chunfeng Lu , Zhiguo Sheng , Gang Liu , Ze Fu , Benzhan Zhu , Shuangqing Peng
DOI:
Received January 05, 2010,Revised March 18, 2010, Accepted , Available online
Volume 23,2011,Pages 119-124
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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 g/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 e ects 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.
