Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2018-07-11 , DOI: 10.1016/j.fct.2018.07.019 Ying-Zhi Zhang , Yu-Zhu Zuo , Zheng-Hai Du , Jun Xia , Cong Zhang , Hui Wang , Xue-Nan Li , Jin-Long Li
Di (2-ethylhexyl) phthalate (DEHP) is a widely distributed pollutant that is of great concern due to its negative health effects. However, whether DEHP exposure causes liver toxicity in birds remains unclear. To clarify the potential hepatotoxicity of DEHP, quails were exposed to 0, 250, 500 and 1000 mg/kg BW/day DEHP by gavage treatment for 45 days. The livers of DEHP-exposed quails showed histomorphological changes. DEHP exposure induced a significant increase in cytochrome P450 enzyme system (CYP450s) activity (including aniline-4-hydroxylase (AH), aminopyrine N-demethylase (APND), erythromycin N-demethylase (ERND) and NADPH-cytochrome C reductase (NCR)) and in the contents of total cytochrome P450 (CYP450) and cytochrome b5 (Cyt b5) in quail liver. DEHP exposure also influenced the expression of nuclear xenobiotic receptors (NXRs) and CYP450 isoforms in the liver. The results suggested that DEHP-induced hepatotoxicity in quail liver is associated with activation of the NXRs pathway responses and disruption of CYP450s homeostasis. This study will help to further elucidate DEHP exposure-induced liver toxicity in quails.
中文翻译:
邻苯二甲酸二(2-乙基己基)酯(DEHP )通过触发核外源生物受体和调节细胞色素P450系统诱导鹌鹑(Coturnix japonica)的肝毒性
邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种分布广泛的污染物,由于其对健康的负面影响而备受关注。但是,DEHP暴露是否会引起家禽肝毒性尚不清楚。为了阐明DEHP的潜在肝毒性,将鹌鹑通过管饲法暴露于0、250、500和1000 mg / kg BW /天的DEHP中,持续45天。暴露于DEHP的鹌鹑的肝脏表现出组织形态学变化。暴露于DEHP会引起细胞色素P450酶系统(CYP450s)活性(包括苯胺-4-羟化酶(AH),氨基比林N-脱甲基酶(APND),红霉素N-脱甲基酶(ERND)和NADPH-细胞色素C还原酶(NCR)的活性显着增加。 )和鹌鹑肝脏中总细胞色素P450(CYP450)和细胞色素b5(Cyt b5)的含量。DEHP暴露也影响了核异源受体(NXRs)的表达和肝脏中的CYP450亚型。结果表明,DEHP诱导的鹌鹑肝毒性与NXRs通路反应的激活和CYP450稳态的破坏有关。这项研究将有助于进一步阐明DEHP暴露引起的鹌鹑肝脏毒性。