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Arch Med Res. 2009 Apr;40(3):139-45. doi: 10.1016/j.arcmed.2009.02.006. Epub 2009 Apr 8.

Long-term treatments with low- and high dose olanzapine change hepatocyte numbers in rats. A stereological and histopathological study.

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  • 1Department of Histology and Embryology, Karadeniz Technical University School of Medicine, Trabzon, Turkey.



Olanzapine, an atypical antipsychotic agent, has been commonly used to treat schizophrenia and bipolar mania because it demonstrates better efficacy for negative schizophrenic symptoms and has minimal extrapyramidal side effects compared to typical antipsychotic drugs. Recent reports of serious hepatotoxicity induced by olanzapine have been published. In this study we aimed to evaluate the effects of long-term administration of low and high doses of olanzapine on rat livers.


Rats were divided into a control group (n = 5) (CG), a low-dose olanzapine group (n = 5) (LOG) and a high-dose olanzapine group (n = 5) (HOG). Olanzapine in doses of 2 and 4 mg/kg daily for 6 weeks were intraperitoneally injected into the LOG and HOG, respectively. The 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, livers were evaluated stereologically and histopathologically.


Significant differences only in the total number of hepatocytes in the rats' livers were found between CG, and LOG and HOG (p <0.05). The livers' general architecture appeared normal in CG, LOG and HOG.


Findings of the present study indicate that either low or high doses of olanzapine damaged the rat livers at a cellular level.

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