Introduction: Short-term ( < 45 days) treatment studies in rats have reported increased oxidative stress and oxidative (i.e., oxygen free radical-mediated) neural cell injury with haloperidol but not with the atypicals such as clozapine, olanzapine or risperidone (atypical antipsychotics) Therefore, understanding on the expres- sion of antioxidant enzymes and oxidative kidney injury in rats may be important to explain the possible differential mechanisms underlying their clinical and side effects profiles. Generation of reactive oxygen species (ROS) such as hydrogen peroxide, super- oxide radicals, hydroxyl radicals and lipid peroxides are known to damage various cellular components including membrane lipids, protein, DNA and thereby contribute to cellular dysfunction. In this study, effects of the three antipsychotropic drugs, haloperidol, risperidone and olanzapine on lipid peroxidation and some oxidant and antioxidant enzyme activities in rat were studied in kidney.

Materials and Methods: Haloperidol (0.4 and 0.8 mg/kg), risperidone (0.5 and 1 mg/kg), and olanzapine (2 and 4 mg/kg) were administrered intraperitoneally to rats once a day for 6 weeks. There were 6 rats for each subgroup and also in the control which did not receive any drug. Malondialdehyde (MDA) level, and the activities of xanthine oxidase, superoxide dismutase, catalase (Cat) and glutathione peroxidase (GPx) in kidney tissue were measured by spectrophotometric methods. The differences among the means of the first and second doses were evaluated by One-way ANOVA with post-hoc LSD test, seperately. The difference between first and second doses was tested by Mann- Whitney U test. P < 0.05 was accepted as the level of statistical significance.
Results: Haloperidol, risperidone and olanzapine did not affect MDA level in both dose levels. Haloperidol increased the GPx activity in both dose levels. Cat and GPx levels were higher in high haloperidol dose compared with low dose. Risperidone increased the SOD and GPx activities at low dose. There were no difference between the two doses. Olanzapine decreased Cat activity, while it increased GPx at low dose. SOD and Cat activities were higher at high dose of olanzapine.

Discussion and conclusion: Our results demonstrated that these three antipsychotic drugs does not increase lipid peroxidation in kidney tissue in the doses administered in this study. However, all three drugs increased the GPx activity at low dose level, while only haloperidol increased the GPx activity at high dose also. Risperidone increased the SOD at low dose only, and olanzapine decreased the Cat activity at low dose.