Mechanisms of Phenytoin-Induced Toxicity in Freshly Isolated Rat Hepatocytes and the Protective Effects of Taurine and/or Melatonin
Article first published online: 3 DEC 2013
© 2013 Wiley Periodicals, Inc.
Journal of Biochemical and Molecular Toxicology
Volume 28, Issue 3, pages 111–118, March 2014
How to Cite
Eghbal, M. A., Taziki, S. and Sattari, M. R. (2014), Mechanisms of Phenytoin-Induced Toxicity in Freshly Isolated Rat Hepatocytes and the Protective Effects of Taurine and/or Melatonin. J. Biochem. Mol. Toxicol., 28: 111–118. doi: 10.1002/jbt.21542
- Issue published online: 4 MAR 2014
- Article first published online: 3 DEC 2013
- Manuscript Accepted: 1 NOV 2013
- Manuscript Revised: 15 OCT 2013
- Manuscript Received: 15 AUG 2013
- Students’ Research Committee of Tabriz University of Medical Sciences
- Isolated Rat Hepatocytes;
- Melatonin, Taurine;
Phenytoin is a widely used antiepileptic drug. However, hepatotoxicity is one of its adverse effects reported in some patients. The mechanism(s) by which phenytoin causes hepatotoxicity is not clear yet. This study was designed to evaluate the cytotoxic mechanism(s) of phenytoin toward rat hepatocytes (whose cytochrome P450 enzymes had been induced by Phenobarbital). Furthermore, the effect of taurine and/or melatonin on this toxicity was investigated. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation (LPO), and mitochondrial depolarization were monitored as toxicity markers. Results showed that phenytoin caused an elevation in ROS formation, depletion of intracellular reduced glutathione, increase in cellular oxidized glutathione, enhancement of LPO, and mitochondrial damage. Taurine (1 mM) and/or melatonin (1 mM) administration decreased the intensity of cellular injury caused by phenytoin. This study suggests the protective role of taurine and/or melatonin against phenytoin-induced cellular damage probably through their reactive radical scavenging properties and their effects on mitochondria.