Mitochondrial energy metabolism impairment and liver dysfunction following chronic exposure to dichlorvos
Mitochondrial energy metabolism impairment and liver dysfunction following chronic exposure to dichlorvos
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DOI：
10.1016/j.tox.2010.01.017
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发表时间：
2010-04-11
期刊：
影响因子：
4.5
通讯作者：
Gill, Kiran Dip
中科院分区：
文献类型：
--
作者：
Binukumar, B. K.;Bal, Amanjit;Gill, Kiran Dip
尽管急性农药中毒的影响众所周知，但几乎没有任何关于长期低水平接触后对健康影响的数据。尚未解决的主要问题包括在没有中毒的情况下适度接触的影响。本研究阐明了慢性有机磷暴露（敌敌畏6 mg/kg b.w.，S.C. 12周）导致肝功能障碍。线粒体是细胞能量产生和氧消耗的主要部位，是有机磷中毒的可能靶点。因此，本研究的目的是探讨慢性敌敌畏暴露对肝脏线粒体电子传递链（ETC）的影响，线粒体钙摄取及其对肝酶和肝功能障碍的诱导作用。我们的研究结果表明，线粒体电子传递活动的细胞色素氧化酶沿着改变线粒体复合物I和II的活动。这种电子传递复合物的活动的减少反过来影响ATP的合成和ATP水平不利地从敌敌畏（DDVP）处理的大鼠肝脏中分离的线粒体。DDVP处理的大鼠肝脏线粒体制备物显示线粒体Ca 2+摄取显著增加，ROS水平升高。线粒体钙摄取、线粒体电子转移酶活性的改变和ROS水平的升高可能依次引起肝酶（ALT、AST和ALP）的升高。电镜下观察到DDVP染毒12周后肝细胞线粒体和细胞核的形态学变化。这些研究提供了线粒体生物能量学受损的证据，这可能导致慢性暴露于敌敌畏后的肝功能障碍。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Although the effects of acute pesticide poisoning are well known but, hardly any data exists regarding the health effects after long-term low-level exposure. Major unresolved issues include the effect of moderate exposure in the absence of poisoning. The present study elucidates a possible mechanism by which chronic organophosphate exposure (dichlorvos 6 mg/kg b.wt., s.c. for 12 weeks) causes liver dysfunction. Mitochondria, a primary site of cellular energy generation and oxygen consumption represent a likely target for organophosphate poisoning. Therefore, the objective of the current study was planned with an aim to investigate the effect of chronic dichlorvos exposure on liver mitochondrial electron transport chain (ETC), mitochondrial calcium uptake and its implications on the induction of liver enzymes and liver dysfunction in rodent model. Our results indicated decreased mitochondrial electron transfer activities of cytochrome oxidase along with altered mitochondrial complexes I and II activity. This decrease in the activities of electron transport complexes in turn affected the ATP synthesis and ATP levels adversely in the mitochondria isolated from dichlorvos (DDVP) treated rat liver. Mitochondrial preparation from DDVP treated rat liver demonstrated significant increase in mitochondrial Ca2+ uptake and increase ROS levels. The alterations in the mitochondrial calcium uptake, mitochondrial electron transfer enzyme activities and increase ROS levels in turn might have caused an increase in liver enzymes (ALT, AST and ALP). The electron micrographs of liver cells depicted morphological changes in mitochondria as well as nucleus following 12 weeks of exposure to DDVP. These studies provide an evidence of impaired mitochondrial bioenergetics which may lead to liver dysfunction after chronic exposure to dichlorvos. (C) 2010 Elsevier Ireland Ltd. All rights reserved.