Mechanisms of the Statins Cytotoxicity in Freshly Isolated Rat Hepatocytes

ABSTRACT Statins are potent drugs, used as lipid‐lowering agents in cardiovascular diseases. Hepatotoxicity is one of the serious adverse effects of statins, and the exact mechanism of hepatotoxicity is not yet clear. In this study, the cytotoxic effects of the most commonly used statins, that is, a...

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Published in:Journal of biochemical and molecular toxicology 2013-06, Vol.27 (6), p.287-294
Main Authors: Abdoli, Narges, Heidari, Reza, Azarmi, Yadollah, Eghbal, Mohammad Ali
Format: Article
Language:English
Subjects:
Animals
Atorvastatin Calcium
Cell Death - drug effects
Cell Survival - drug effects
Glutathione - metabolism
Glutathione Disulfide - metabolism
Gutathione
Hepatocytes - drug effects
Hepatocytes - metabolism
Hepatocytes - pathology
Hepatotoxicity
Heptanoic Acids - toxicity
Hydroxymethylglutaryl-CoA Reductase Inhibitors - toxicity
Lipid Peroxidation - drug effects
Lovastatin - toxicity
Male
Membrane Potential, Mitochondrial - drug effects
Mitochondrial Membrane Potential
Oxidative Stress
Pyrroles - toxicity
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species - metabolism
ROS Formation
Simvastatin - toxicity
Statins
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Summary:ABSTRACT Statins are potent drugs, used as lipid‐lowering agents in cardiovascular diseases. Hepatotoxicity is one of the serious adverse effects of statins, and the exact mechanism of hepatotoxicity is not yet clear. In this study, the cytotoxic effects of the most commonly used statins, that is, atorvastatin, lovastatin, and simvastatin toward isolated rat hepatocytes, were evaluated. Markers, such as cell death, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential, and the amount of reduced and oxidized glutathione in the statin‐treated hepatocytes, were investigated. It was found that the statins caused cytotoxicity toward rat hepatocytes dose dependently. An elevation in ROS formation, accompanied by a significant amount of lipid peroxidation and mitochondrial depolarization, was observed. Cellular glutathione reservoirs were decreased, and a significant amount of oxidized glutathione was formed. This study suggests that the adverse effect of statins toward hepatocytes is mediated through oxidative stress and the hepatocytes mitochondria play an important role in the statin‐induced toxicity. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:287‐294, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21485
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.21485