A novel nuclear xenobiotic receptors (AhR/PXR/CAR)-mediated mechanism of DEHP-induced cerebellar toxicity in quails (Coturnix japonica) via disrupting CYP enzyme system homeostasis

作者：Du, Zheng-Hai; Xia, Jun; Sun, Xiao-Chen; Li, Xue-Nan; Zhang, Cong; Zhao, Hua-Shan; Zhu, Shi-Yong; Li, Jin-Long^*

来源：Environmental Pollution, 2017, 226: 435-443.

DOI：10.1016/j.envpol.2017.04.015

• DEHP
• Quail
• Cerebellum injury
• NXRs response
• CYP enzyme system homeostasis
• AhR/PXRICAR pathway

Di-(2-ethylhexyl)-phthalate (DEHP) is causing serious health hazard in wildlife animal and human through environment and food chain, including the effect of brain development and impacted neuro-behavioral outcomes. However, DEHP exposure caused cerebellar toxicity in bird remains unclear. To evaluate DEHP-exerted potential neurotoxicity in cerebellum, male quails were exposed with 0, 250, 500 and 750 mg/kg BW/day DEHP by gavage treatment for 45 days. Neurobehavioral abnormality and cerebellar histopathological alternation were observed in DEHP-induced quails. DEHP exposure increased the contents of total Cytochrome P450s (CYPs) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c reductase (NCR) and aniline-4-hydeoxylase (AH) in quail cerebellum. The expression of nuclear xenobiotic receptors (NXRs) and the transcriptions of CYP enzyme isoforms were also influenced in cerebellum by DEHP exposure. These results suggested that DEHP exposure caused the toxic effects of quail cerebellum. DEHP exposure disrupted the cerebellar CYP enzyme system homeostasis via affecting the transcription of CYP enzyme isoforms. The cerebellar P450arom and CYP3A4 might be biomarkers in evaluating the neurotoxicity of DEHP in bird. Finally, this study provided new evidence that DEHP-induced toxic effect of quail cerebellum was associated with activating the NXRs responses and disrupting the CYP enzyme system homeostasis.

• 出版日期2017-7
• 单位东北农业大学