title: Protective effect of NAC against malathion-induced oxidative stress in freshly isolated rat hepatocytes.
abstract: OBJECTIVE
  Induction of oxidative stress by Organophosphate compounds (OPs) has been previously reported. In the present work, the mechanism of protective effects of N-acetylcysteine as a glutathion (GSH) prodrug against malathion-induced cell toxicity was investigated. In this work, freshly isolated rat hepatocytes were used to determine the effect of NAC on malathion-induced cytotoxicity, formation of reactive oxygen species (ROS) and mitochondrial dysfunction.
  
  
  METHODS
  Rat hepatocytes were isolated using collagenase perfusion and then cell viability, mitchondrial membrane potential (MMP) and ROS formation were determined using trypan blue exclusion, Rhodamine 123 fluorescence and fluorogenic probe, 2', 7' -dichlorofluorescin diacetate (DCFH-DA), respectively.
  
  
  RESULTS
  Despite the protective effect of NAC on malathion-induced cell toxicity and MMP dysfunction, its efficacy against ROS formation was not adequate to completely protect the cells.
  
  
  CONCLUSIONS
  Cytotoxic effects of malathion regardless of its cholinergic feature, is started with gradual free radical production but, the main factor that causes cell death, is mitochondrial dysfunction, so that reduction of ROS formation alone is not sufficient for cell survival, and the maintenance of mitochondrial integrity through different mechanisms is the most ameliorative factor specially at high levels of cell damage, as NAC seemed to protect cells with various fashions apart from ROS scavenging in concentrations higher than malathion's LC50.
authors: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. ; Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Sara
authors: S
authors: Mostafalou
authors: Mohammad
authors: M
authors: Abdollahi
authors: Mohammad Ali
authors: MA
authors: Eghbal
authors: Nazli
authors: N
authors: Saeedi Kouzehkonani
keywords: Cytotoxicity; Hepatocytes; Mitochondria; N-actylcycteine; Organophosphate Pesticides; Oxidative Stress