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
| Autor: | Cong Zhang, Xiao-Chen Sun, Xue-Nan Li, Zheng-Hai Du, Jun Xia, Hua-Shan Zhao, Jin-Long Li, Shi-Yong Zhu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine endocrine system medicine.medical_specialty Cerebellum Health Toxicology and Mutagenesis Receptors Cytoplasmic and Nuclear Coturnix 010501 environmental sciences Toxicology Quail 01 natural sciences Xenobiotics 03 medical and health sciences chemistry.chemical_compound Aromatase Cytochrome P-450 Enzyme System Diethylhexyl Phthalate biology.animal Internal medicine medicine Animals Homeostasis Humans 0105 earth and related environmental sciences Pregnane X receptor CYP3A4 biology Neurotoxicity General Medicine medicine.disease biology.organism_classification Pollution 030104 developmental biology medicine.anatomical_structure Endocrinology Receptors Aryl Hydrocarbon chemistry Toxicity Xenobiotic |
| Zdroj: | Environmental Pollution. 226:435-443 |
| ISSN: | 0269-7491 |
| DOI: | 10.1016/j.envpol.2017.04.015 |
| Popis: | 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 neurobehavioral 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. |
| Databáze: | OpenAIRE |
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