Nephrotoxic Effects of Chronically Administered Olanzapine and Risperidone in Male Rats

Abstract

Objective: Olanzapine and risperidone are members of the atypical antipsychotic family. Even though they are widely used for the treatment of a broad range of symptoms and disorders in psychiatric practice, their effects on kidney are little known. Nevertheless, the toxic features of these medicines on the tissues, organs or systems other than the kidneys have been demonstrated previously. For these reasons, we aimed to evaluate the effects of long-term administration of low- and high-doses of olanzapine and risperidone on rat kidneys in the present study. Methods: Twenty five rats were divided into 5 groups equally: a control group (CG), a low-dose olanzapine group (LOG), a high-dose olanzapine group (HOG), a low-dose risperidone group (LRG), and a high-dose risperidone group (HRG). Olanzapine in doses of 0.5 and 2.5 mg/kg daily for 6 weeks were intraperitoneally injected into the LOG and HOG, respectively. Similarly, risperidone in doses of 0.5 and 1 mg/kg daily for 6 weeks were intraperitoneally injected into the LRG and HRG, respectively. Same volume and dosages of normal saline (0.9% NaCl) were given to the CG during the same period. At the end of the experiment, the kidneys were dissected out and evaluated histopathologically. Results: Although there were any abnormalities in the LOG, it was determined significant nephrotoxic effects, including losing regularities in both tubular and glomerular structure of kidneys, focal necrosis in some area of renal cortex and medulla, cells with pyknotic nuclei and eosinophilic cytoplasm in both glomerular capillaries and mesangium, an increase in thickness of basal membrane of intraglomerular capillary, especially in parietal layer of Bowman’s capsule, and in some fields, abnormalities caused by the loss of tubule cells, such as hydropic vacuolization and eosinophilic accumulations in the HOG, LRG, and HRG. Conclusion: Albeit it has been hypothesized that these nephrotoxic effects are due to the oxidative stress and mitochondrial dysfunction associated antipsychotic treatment, the definite mechanisms of the nephrotoxicity continue uncertain. On the other hand, nephrotoxicity that presents with cells and casts in the urine, oliguria, proteinuria, elevated serum creatinine, and elevated urea may occur easily in some individuals and these agents should be used cautiously, particularly in patients with renal disease. Because some toxicity here is dose-dependent, there might be an advantage of preferring minimum therapeutic doses with chronic administration to decrease their side effects on the kidney in these special conditions. However, further research is surely needed to study the causal relationship between atypical antipsychotic use and nephrotoxicity.