This study investigated the effect of chronic neuroleptic therapy on hepatic glutathione concentration in relation to lipid peroxidation. Hepatic malondialdehyde (MDA) and glutathione (GSH) concentrations were measured in liver biopsies from a group of patients receiving chronic psychotropic drug therapy. The results were compared with values obtained from a selected group of controls and correlated to liver histology and blood biochemistry. Patients taking neuroleptics exhibited increased hepatic MDA and decreased total GSH levels when compared with controls. The reduction of GSH was accompanied by a 25% increase in oxidized glutathione (GSSG) concentrations. In addition, a positive correlation between liver MDA and GSSG concentrations was observed in the group receiving neuroleptic therapy. The study results suggest that an increased lipid peroxidation may represent a contributory mechanism for neuroleptic drug toxicity.
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