In vitro/vivo studies towards mechanisms of risperidone-induced oxidative stress and the protective role of coenzyme Q10 and N-acetylcysteine

Abstract

The hepatotoxic effects of the antipsychotic agent, risperidone (RIS) were investigated for better understanding the pathogenesis of RIS in liver toxicity in vivo and in in vitro. Isolated rat hepatocytes were obtained by collagenase perfusion technique and were then incubated with RIS, different antioxidants in particular coenzyme Q10 (CoQ10), N-acetyl cysteine (NAC). Our results showed that RIS could induce cytotoxicity via rising reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation. All of these effects were significantly (p < 0.05) inhibited by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate (ATP) generators. Similar outcomes were obtained from the in vivo experiments. Liver function enzyme test and histopathological evaluation confirmed RIS-(6 mg/kg) induced damage. Based on these results, it is suggested that RIS-induced liver toxicity is associated with mitochondrial/lysosomal cross-talk following the initiation of oxidative stress. Thus, the use of CoQ10 and/or NAC seems to be a safe therapeutic option in this context.

Keywords:

• Coenzyme Q10
• hepatotoxicity
• oxidative stress
• Risperidone
• ROS formation

Acknowledgments

The authors are grateful to Dr. H. Hamzeiy for proofreading the manuscript. The authors would like to thank Drug Applied Research Center of Tabriz University of Medical Sciences, Tabriz, Iran, for providing technical facilities. The authors are also thankful to the University’s “Students’ Research Committee” for providing technical supports to the study.

Disclosure statement

The authors declare that there are no conflicts of interest associated with this work.

Funding information

This is a report of a database from thesis entitled “Evaluation of the mechanisms of hepatic injuries induced by antipsychotic drugs” registered in “Drug Applied Research Center”(Grant number: 101/93)