title: In vitro effect of N-acetylcysteine on hepatocyte injury caused by dichlorodiphenyltrichloroethane and its metabolites.
abstract: The organochlorine pesticide, dichlorodiphenyltrichloroethane (DDT), is still used to combat the spread of malaria in several developing countries despite its accumulation and known hepatotoxic effects that have been demonstrated both in vitro and in vivo. N-Acetylcysteine (NAC) is a recognized hepatoprotective agent that has been reported to reduce hepatotoxicity initiated by many different compounds. The aim of this study was to determine whether NAC could counter in vitro hepatocyte injury induced by DDT or its two major metabolites, dichlorodiphenyldichloroethylene and dichlorodiphenyldichloroethane. HepG2 cell cultures were used to assess the following parameters of toxicity: cellular viability, intracellular levels of reactive oxygen species (ROS), mitochondrial membrane potential and initiation of apoptosis. None of the three test compounds induced ROS generation, yet exposure to any of the three compounds produced mitochondrial hyperpolarization, which was countered by NAC pretreatment. All three test compounds also induced apoptotic cell death, which was inhibited by NAC. Despite NAC counteracting some adverse intracellular changes due to organochlorine exposure, it appeared to aggravate the cytotoxic effects of the organochlorine compounds at low test concentrations. As the same outcome may also occur in vivo, results from the present study raise concern about the use of NAC as treatment for DDT-induced hepatotoxicity.
authors.affiliation: 1Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: J J
authors.initials: JJ
authors.lastname: van Tonder
authors.forename: M
authors.initials: M
authors.lastname: Gulumian
authors.forename: A D
authors.initials: AD
authors.lastname: Cromarty
authors.forename: V
authors.initials: V
authors.lastname: Steenkamp
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003634:DDT / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000633:toxicity; D003633:Dichlorodiphenyl Dichloroethylene / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000633:toxicity; D003632:Dichlorodiphenyldichloroethane / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000633:toxicity; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007306:Insecticides / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007700:Kinetics; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects; D009994:Osmolar Concentration; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D007306:Insecticides; D020011:Protective Agents; D017382:Reactive Oxygen Species; D003633:Dichlorodiphenyl Dichloroethylene; D003634:DDT; D003632:Dichlorodiphenyldichloroethane; D000111:Acetylcysteine
keywords: DDT; N-acetylcysteine; ROS; apoptosis; hepatotoxicity; mitochondria