Activating nuclear xenobiotic receptors and triggering ER stress and hepatic cytochromes P450 systems in quails (Coturnix C-coturnix) during atrazine exposure

作者：Du, Zheng-Hai; Qin, Lei; Lin, Jia; Sun, Yan-Chun; Xia, Jun; Zhang, Cong; Li, Xue-Nan; Li, Jin-Long^*

来源：Environmental Toxicology, 2017, 32(6): 1813-1822.

DOI：10.1002/tox.22404

• atrazine
• hepatotoxicity
• cytochromes P450 enzyme systems
• endoplasmic reticulum stress
• nuclear xenobiotic receptors response

Atrazine (ATR) is one of the most widely detected contaminant in the ecosystem. Nuclear xenobiotic receptors are activated by herbicides and induce the transcription of CYP450 isoforms involved in xenobiotic metabolism and transport. However, little is known about hepatic nuclear xenobiotic receptors in birds are responsible for ATR-induced hepatotoxicity via regulating the cytochrome P450 enzyme systems (CYP450s). The objective of this study was to investigate the mechanism of ATR hepatotoxicity in quails. For this purpose, male quails were dosed by oral gavage from sexual immaturity to maturity with 0, 50, 250, and 500mg/kg/day ATR for 45days. The results showed that ATR exposure caused the hepatotoxicity damage and endoplasmic reticulum (ER) degeneration. It suggested that ER is a target organelle of ATR toxicity in hepatocytes. ATR exposure disrupted the hepatic CYP450s homeostasis. This study also demonstrated that ATR triggered the CYP450 isoforms transcription via activating the hepatic CAR/PXR pathway. The present study provides new insights regarding the mechanism of the ATR-induced hepatotoxicity through activating nuclear xenobiotic receptors and triggering ER stress and hepatic CYP450s in quails.

• 出版日期2017-6
• 单位中国水产科学研究院; 东北农业大学; 齐齐哈尔医学院