Enhanced hepatotoxicity induced by repeated exposure to polychlorinated
biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin in combination in male rats |
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Authors: | Yimei Wang Chunfeng Lu Zhiguo Sheng Gang Liu Ze Fu Benzhan Zhu and Shuangqing Peng |
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Institution: | 1. Evaluation and Research Center for Toxicology,Institute of Disease Control and Prevention,Academy of Military Medical Sciences,Beijing 100071,China 2. Evaluation and Research Center for Toxicology,Institute of Disease Control and Prevention,Academy of Military Medical Sciences,Beijing 100071,China; Department of Pharmacology,Basic Medical College,Jiamusi University,Jiamusi 154007,China 3. State Key Laboratory of Environmental Chemistry and Ecotoxicology,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China |
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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 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. |
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Keywords: | 2 3 7 8-tetrachlorodibenzo-p-dioxin polychlorinated biphenyls combined exposure hepatotoxicity |
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