Atrazine Triggers Mitochondrial Dysfunction and Oxidative Stress in Quail ( Coturnix C. coturnix) Cerebrum via Activating Xenobiotic-Sensing Nuclear Receptors and Modulating Cytochrome P450 Systems
| Autor: | Jun Xia, Hua-Shan Zhao, Xue-Nan Li, Lei Qin, Cong Zhang, Jia Lin, Jin-Long Li |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Receptors Cytoplasmic and Nuclear Apoptosis Coturnix 010501 environmental sciences Mitochondrion medicine.disease_cause 01 natural sciences Xenobiotics Avian Proteins 03 medical and health sciences Cytochrome P-450 Enzyme System biology.animal medicine Animals Homeostasis Cerebrum 0105 earth and related environmental sciences biology Chemistry Herbicides Neurotoxicity Cytochrome P450 General Chemistry medicine.disease biology.organism_classification Quail Cell biology Mitochondria Oxidative Stress 030104 developmental biology Toxicity biology.protein Atrazine General Agricultural and Biological Sciences Oxidative stress |
| Zdroj: | Journal of agricultural and food chemistry. 66(25) |
| ISSN: | 1520-5118 |
| Popis: | The residues from the widely used broad-spectrum environmental herbicide, atrazine (ATR), result in the exposure of nontarget organisms and persist as a global major public health hazard. ATR is neurotoxic and may cause adverse health effects in mammals, birds, and fishes. Nevertheless, the molecular mechanism of ATR induced neurotoxicity remains unclear. To assess the molecular mechanisms of ATR-induced cerebral toxicity through potential oxidative damage, quail were treated with ATR by oral gavage administration at doses of 0, 50, 250, and 500 mg/kg body weight daily for 45 days. Markedly, increases in the amount of swelling of neuronal cells, the percentage of mean damaged mitochondria, mitochondrial malformation, and mitochondrial vacuolar degeneration as well as decreases in the mitochondrial cristae and mitochondrial volume density were observed by light and electron microscopy in the cerebrum of quail. ATR induced toxicities in the expression of mitochondrial function-related genes and promoted oxidative damage, as indicated by effects on oxidative stress indices. These results indicated that ATR exposure can cause neurological disorders and cerebral injury. ATR may initiate apoptosis by activating Bcl-2, Bax, and Caspase3 protein expression but failed to induce autophagy (LC3B has not cleaved to LC3BI/II). Furthermore, ATR induced CYP-related enzymes metabolism disorders by activating the nuclear xenobiotic receptors response (NXRs including AHR, CAR, and PXR) and increased expression of several CYP isoforms (including CYP1B1 and CYP2C18) and thereby producing mitochondrial dysfunction. In this study, we observed ATR exposure resulted in oxidative stress and mitochondrial dysfunction by activating the NXR response and interfering the CYP450s homeostasis in quail cerebrum that supported the molecular mechanism of ATR induced cerebrum toxicity. In conclusion, these results provided new evidence on molecular mechanism of ATR induced neurotoxicity. |
| Databáze: | OpenAIRE |
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