Mitochondrial energy metabolism impairment and liver dysfunction following chronic exposure to dichlorvos

Toxicology. 2010 Apr 11;270(2-3):77-84. doi: 10.1016/j.tox.2010.01.017. Epub 2010 Feb 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Apoptosis / drug effects
  • Calcium / metabolism
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Dichlorvos / toxicity*
  • Electron Transport / drug effects
  • Electron Transport Complex IV / metabolism
  • Energy Metabolism / drug effects*
  • Insecticides / toxicity*
  • Liver Function Tests
  • Male
  • Microscopy, Electron
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism*
  • NADH Dehydrogenase / metabolism
  • Oxidative Phosphorylation / drug effects
  • Oxygen Consumption / drug effects
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism

Substances

  • Insecticides
  • Reactive Oxygen Species
  • Dichlorvos
  • Adenosine Triphosphate
  • NADH Dehydrogenase
  • Electron Transport Complex IV
  • Adenosine Triphosphatases
  • Calcium