title: 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.
authors.affiliation: a Biotechnology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|b Drug Applied Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|c Pharmacology and Toxicology Department , School of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran.|d Students' Research Committee , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Aziz
authors.initials: A
authors.lastname: Eftekhari
authors.affiliation: b Drug Applied Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|c Pharmacology and Toxicology Department , School of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Ahmadian
authors.affiliation: b Drug Applied Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|c 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: b Drug Applied Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|c Pharmacology and Toxicology Department , School of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Parvizpur
authors.affiliation: b Drug Applied Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Hamishehkar
authors.affiliation: b Drug Applied Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|c Pharmacology and Toxicology Department , School of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Eghbal
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000633:toxicity*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014451:Ubiquinone; C024989:coenzyme Q10; D018967:Risperidone; D000111:Acetylcysteine
keywords: Coenzyme Q10; ROS formation; Risperidone; hepatotoxicity; oxidative stress