Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney

Abstract

The use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effectson the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverseeffects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats weretreated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily doserecommended for antipsychotic drug therapy. The expression and activities of antioxidantenzymes superoxide dismutase (SOD) type 1 and type 2, catalase (CAT), glutathione reductase(GR), and glutathione S-transferases (GSTs) activity were measured in the kidneys. Changes in thekidneys were also evaluated histologically. Ziprasidone, CLO, and SER reduced renal SOD type 1and type 2 activities. Decreased CAT activity was observed only in SER-treated rats. An inhibitionin GR activity and increased activity of GST was found only after treatment with CLO. Histologicalanalysis showed dilatation of proximal tubules in kidneys with all three drugs. In conclusion, dataindicate that redox disturbances may contribute to renal morphologic alterations in proximaltubules in rats treated with all APD.