title: Activating nuclear xenobiotic receptors and triggering ER stress and hepatic cytochromes P450 systems in quails (Coturnix C. coturnix) during atrazine exposure.
abstract: 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 500 mg/kg/day ATR for 45 days. 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.
authors.affiliation: Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Zheng-Hai
authors.initials: ZH
authors.lastname: Du
authors.affiliation: Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, 150030, People's Republic of China.|Laboratory animal centre, Qiqihar Medical University, Qiqihar, 161006, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qin
authors.affiliation: Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Lin
authors.affiliation: Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin, 150070, People's Republic of China.
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Sun
authors.affiliation: Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.affiliation: Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, 150030, People's Republic of China.|Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, 150030, People's Republic of China.|Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Xue-Nan
authors.initials: XN
authors.lastname: Li
authors.affiliation: Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, 150030, People's Republic of China.|Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Li
mesh_terms: D000818:Animals; D001280:Atrazine / Q000493:pharmacokinetics / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D003370:Coturnix / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015262:Xenobiotics / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D018160:Receptors, Cytoplasmic and Nuclear; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D001280:Atrazine
keywords: atrazine; cytochromes P450 enzyme systems; endoplasmic reticulum stress; hepatotoxicity; nuclear xenobiotic receptors response