title: Performance of a novel atrazine-induced cerebellar toxicity in quail (Coturnix C. coturnix): Activating PXR/CAR pathway responses and disrupting cytochrome P450 homeostasis.
abstract: Atrazine is well known to be a biologically hazardous substance with toxic effects, but atrazine-induced neurotoxicity remains unclear. The aim of this study was to investigate the mechanisms of atrazine-induced cerebellar toxicity. To determine atrazine-exerted potential neurotoxicity, quails were treated with 50, 250 and 500 mg/kg atrazine by gavage administration for 45 days. Notably, the changes of cytochrome P450 enzyme system (CYP450s) were observed in atrazine-exposed quails. The contents of cytochrome P450 (CYP450) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c reductase (NCR), aminopyrin N-demethylase (APND) and aniline-4-hydeoxylase (AH) were increased and erythromycin N-demethylase (ERND) was decreased in quail cerebellum. Nuclear xenobiotic receptors (NXRs) and the transcriptions of NXRs-related target molecules were influenced in cerebellum. Atrazine disrupted the CYP450s balance in quail cerebellum. These results suggested that atrazine-induced cerebellar toxicity in birds was associated with activating PXR/CAR pathway responses and disrupting cytochrome P450 homeostasis. This study provided novel evidences that atrazine exposure induced cerebellar toxicity.
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China; Laboratory Animal Center, Qiqihar Medical University, Qiqihar, 161006, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qin
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Zheng-Hai
authors.initials: ZH
authors.lastname: Du
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Lin
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
authors.forename: Xue-Nan
authors.initials: XN
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China. Electronic address: Jinlongli@neau.edu.cn.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Li
mesh_terms: D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D002526:Cerebellar Diseases / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D000090702:Constitutive Androstane Receptor; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D006540:Herbicides / Q000633:toxicity; D006706:Homeostasis / Q000187:drug effects*; D000077297:Pregnane X Receptor; D011784:Quail; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000090702:Constitutive Androstane Receptor; D006540:Herbicides; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D003577:Cytochrome P-450 Enzyme System; D001280:Atrazine
keywords: Atrazine; Cytochrome P450 homeostasis; Nuclear xenobiotic receptors response; PXR/CAR pathway; Quail cerebellum