LONG TERM EFFECTS OF OLANZAPINE CUMULATIVE DOSES ON FAT TISSUE. AN EXPERIMENTAL MODEL IN RATS
GEORGE ECHIM1, CĂTĂLINA GABRIELA PISOSCHI2*, CAMIL EUGEN VARI3*, MELINDA KOLCSÀR3, BIANCA EUGENIA ŐSZ3, ZSOLT GÁLL3, CĂLIN CHIBELEAN4, ANCA BERBECARU-IOVAN5, MARIA T. DOGARU3
1Doctoral School, University of Medicine and Pharmacy Tîrgu Mureș, 38 Gh. Marinescu Street, RO-540139, Romania
2Department of Biochemistry, University of Medicine and Pharmacy Craiova, 2-4 Petru Rares Street, RO-200349, Romania
3Department of Pharmacology and Clinical Pharmacy, University of Medicine and Pharmacy Tîrgu Mureș, 38 Gh. Marinescu Street, RO-540139, Romania
4Department of Urology, University of Medicine and Pharmacy Tîrgu Mureș, 38 Gh. Marinescu Street, RO-540139, Romania
5Department of Pharmacology, University of Medicine and Pharmacy Craiova, 2-4 Petru Rares Street, RO-200349, Romania
*corresponding author: c_pisoschi@yahoo.com
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Abstract:
Olanzapine, a second generation antipsychotic drug, is frequently used to treat schizophrenia due to several advantages that it has over classical antipsychotics in terms of side effects. However, the occurrence of certain side effects adverse reactions with regards to long term administration is mentioned in the medical literature. The aim of our study was to investigate the effects of various doses of olanzapine, given for 9 weeks, on body weight and to evaluate the drug’s pharmaco-toxicological tropism related mostly to fat and liver tissues in Wistar rats. Olanzapine was administered by gavage in doses of 0.5, 2.0, 4.0 and 6.0 mg/kgbw, respectively, to 70 adult Wistar rats with body weights ranging from 260 to 330 grams, and other two groups serving as controls received only vehicle solution, without any active ingredient. During the experiment, the animals were weighed weekly, and in the end they were euthanized, when samples from their fatty and liver tissues were taken for subsequent histological analyses. The results indicated a relative weight gain of the animals from all treated groups compared to their initial state, the observed changes being gender and dose related, excepting the 6 mg/kgbw group where toxicity signs were noticed during the study. Histological analyses of adipose and liver tissues revealed obvious and significant irreversible inflammatory alterations after 9 weeks of treatment, correlated with the total cumulated olanzapine dose and with the gender of the animals. High doses of olanzapine caused toxic reactions in the second part of the study.

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