期刊
ENVIRONMENTAL TOXICOLOGY
卷 33, 期 12, 页码 1304-1311出版社
WILEY
DOI: 10.1002/tox.22638
关键词
constitutive androstane receptor; cytochromes P450; glutathione; hepatotoxicity; pyrene
资金
- National Natural Science Foundation of China [31500946]
- Science and Technology Department of Zhejiang Province [2017C33128]
- Department of Medical Technology and Education of Zhejiang Province of China [2016KYA134]
- Science and Technology Bureau of Wenzhou of China [Y20140601]
- Science and Technology Plan Project of Wenzhou of China [Y20150089]
- Wenzhou Medical University [QTJ13011]
Polycyclic aromatic hydrocarbons (PAHs) are a group of persistent organic pollutants primarily formed from the incomplete combustion of carbonaceous materials, and have adverse effects on human health. In this study, we investigated whether pyrene, a PAH consisting of 4 fused benzene rings, has adverse effects on rat. Adult male Sprague-Dawly rats were treated daily by oral gavage with vehicle (corn oil) or pyrene at doses of 375, 750, 1500, or 2200 mg/kg/day for 4 days. The results showed that pyrene caused hepatotoxicity in rats. When compared with the control group, relative liver weights, plasma alanine aminotransferase, and direct bilirubin levels significantly increased after pyrene exposure. Hepatocyte swelling and degeneration and decreased hepatic total glutathione (GSH) levels were also found in pyrene-exposed rats. We further observed that mRNA levels of several hepatic metabolizing enzymes regulated by constitutive androstane receptor (CAR) such as CYP2B1 and CYP2B2 significantly increased in pyrene-exposed rats. These results suggest that decreased GSH levels, elevated hepatic metabolizing enzyme gene expression, and CAR activation are important contributors for pyrene-induced hepatotoxicity in rats. Additionally, we found pyrene significantly induced plasma inflammatory indices including white blood cell and lymphocyte counts. We also observed that pyrene exposure increased relative weight of kidneys and disrupted kidney function with elevated urea and creatinine levels in rats.
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