Mechanisms of phenytoin-induced toxicity in freshly isolated rat hepatocytes and the protective effects of taurine and/or melatonin.
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.
['Eghbal|Mohammad Ali|MA|', 'Taziki|Shohreh|S|', 'Sattari|Mohammad Reza|MR|']
D000818:Animals D016923:Cell Death D002478:Cells, Cultured D005978:Glutathione D022781:Hepatocytes D015227:Lipid Peroxidation D008297:Male D008550:Melatonin D053078:Membrane Potential, Mitochondrial D010672:Phenytoin D020011:Protective Agents D051381:Rats D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species D013654:Taurine
Isolated Rat Hepatocytes Phenytoin Hepatotoxicity Melatonin, Taurine