Introduction: The effects of the three antipsychotropic drugs, haloperidol, risperidone and olanzapine on lipid peroxidation and some oxidant and antioxidant enzyme activities in erythrocytes and plasma in rat were studied.

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 group, which did not receive any drug. Malondialdehyde level (MDA), and the activities of xanthine oxidase (XO), superoxide dismutase (SOD), and glutathione peroxidase (GPX) in erythrocytes and plasma 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.
Results: Haloperidol increased erythrocyte MDA level in low dose but it did not affect it in high dose. While risperidone increased erythrocyte MDA level in high dose but it did not affect it in low dose. Olanzapine did not affect erythrocyte MDA level in both dose levels. All drugs decreased plasma MDA level except haloperidol at low dose. Plasma MDA level in haloperidol with high dose was lower than haloperidol with low dose. Haloperidol increased erythrocyte XO and GPX in both doses, while SOD was not affected. Risperidone increased erythrocyte XO and GPX at low dose, while SOD was not affected at all. Olanzapine increased erythrocyte XO in both dose levels, while SOD and GPX were not affected. Erythrocyte XO activity was lower in low doses of risperidone and olanzapine compared with their high doses. Haloperidol increased plasma XO at high dose, otherwise it did not affect the enzyme activities studied. Risperidone increased plasma XO and SOD activities at both dose levels, while it did not affect GPX activity. Olanzapine increased plasma SOD activity at both dose levels, while it increased XO at high dose only. It did not affect plasma GPX activity at all. Plasma XO activity was higher in high doses of haloperidol and risperidone compared with their low dose.
Discussion and Conclusions: In haloperidole group at low dose, the increase in erythrocye GPX was not enough to prevent lipid peroxidation probably due to increased XO activity, while they neutralised each other at high dose. This neutralisation was also the case at risperidone with low dose. It is intresting that olanzapine did not affect erythrocyte MDA level in both dose levels despite increased XO activity. In plasma, it was interesting that MDA level was decreased despite increased XO activity in haloperidol with high dose group. In risperidone and olanzapine groups, increased plasma SOD activity could be counteracted
against increased XO activity resulting in decreased lipid peroxidation. In conclusion, these three antipsychotic drugs studied generally decreased plasma MDA level while they did not affect it in erythrocytes at the dose levels studied.