title: Protective Effects of N-acetylcysteine Against the Statins Cytotoxicity in Freshly Isolated Rat Hepatocytes.
abstract: OBJECTIVE
  Hepatotoxicity is one of the most important side effects of the statins therapy as lipid-lowering agents. However, the mechanism(s) of hepatotoxicity induced by these drugs is not clearly understood yet, and no hepatoprotective agent has been developed against this complication.
  
  
  METHODS
  The protective effect of N-acetylcysteine (NAC) against statins-induced cytotoxicity was evaluated by using freshly isolated rat hepatocytes. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. This technique is based on liver perfusion with collagenase after removal of calcium ion (Ca2+) with a chelator (ethylene glycol tetra acetic acid (EGTA) 0.5 mM). The level of parameters such as cell death, ROS formation, lipid peroxidation, mitochondrial membrane potential (MMP) in the statins-treated hepatocytes were determined. Additionally, the mentioned markers were assessed in the presence of NAC.
  
  
  RESULTS
  Incubation of hepatocytes with the statins resulted in cytotoxicity characterized by an elevation in cell death, increasing ROS generation and consequently lipid peroxidation and impairment of mitochondrial function. Administration of NAC caused reduction in amount of ROS formation, lipid peroxidation and finally, cell viability and mitochondrial membrane potential (MMP) were improved.
  
  
  CONCLUSIONS
  This study confirms that oxidative stress and consequently mitochondrial dysfunction is one of the mechanisms underlying the statins-induced liver injury and treating hepatocytes by NAC (200 μM) attenuates this cytotoxicity.
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ; Pharmacology and Toxicology Department, School of pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. ; Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Narges
authors.initials: N
authors.lastname: Abdoli
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ; Pharmacology and Toxicology Department, School of pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Yadollah
authors.initials: Y
authors.lastname: Azarmi
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ; Pharmacology and Toxicology Department, School of pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Eghbal
keywords: Hepatotoxicity; Mitochondrial membrane potential; N-acetylcysteine; Reactive oxygen species; Statins
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