Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Toxicology. 2010 Apr 11;270(2-3):77-84. doi: 10.1016/j.tox.2010.01.017. Epub 2010 Feb 1.
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 Ca(2+) 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.
虽然急性农药中毒的影响众所周知，但关于长期低水平暴露后的健康影响几乎没有数据。未解决的主要问题包括在没有中毒的情况下中度暴露的影响。本研究阐明了慢性有机磷暴露（敌百虫 6mg/kg 体重，皮下注射 12 周）导致肝功能障碍的可能机制。线粒体是细胞能量产生和耗氧量的主要场所，是有机磷中毒的一个可能靶点。因此，本研究的目的是计划研究慢性敌百虫暴露对肝脏线粒体电子传递链（ETC）、线粒体钙摄取及其对诱导啮齿动物模型中肝酶和肝功能障碍的影响。我们的结果表明，慢性敌百虫暴露导致细胞色素氧化酶的线粒体电子传递活性降低，同时改变了线粒体复合物 I 和 II 的活性。电子传递复合物活性的这种降低反过来又对从敌百虫（DDVP）处理的大鼠肝脏分离的线粒体中的 ATP 合成和 ATP 水平产生不利影响。DDVP 处理大鼠肝脏的线粒体制剂显示线粒体 Ca(2+)摄取显著增加和 ROS 水平增加。线粒体钙摄取、线粒体电子传递酶活性的改变以及 ROS 水平的增加反过来可能导致肝酶（ALT、AST 和 ALP）增加。暴露于 DDVP 12 周后的肝细胞电子显微镜照片显示了线粒体和细胞核的形态变化。这些研究提供了证据表明，慢性接触敌百虫后，线粒体生物能量学受损可能导致肝功能障碍。
