Olanzapine induced biochemical and histopathological changes after its chronic administration in rats

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• 作者：Rehmat Shah^a ; ^b ; ^{rehmatshah@upesh.edu.pk" class="auth_mail" title="E-mail the corresponding author} ; Fazal Subhan^a ; Gowhar Ali^a ; Ihsan Ullah^c ; Sami Ullah^a ; Muhammad Shahid^a ; ^d ; Nisar Ahmad^a ; Khwaja Fawad^a
• 关键词：Olanzapine ; Antipsychotics ; Rats ; Hyperglycemia ; Pancreas ; Toxicity
• 刊名：Journal of the Saudi Pharmaceutical Society
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：24
• 期：6
• 页码：698-704
• 全文大小：2664 K

文摘

Objective: Olanzapine is a second generation antipsychotic acting mainly as a dopamine D₂ and serotonine 5-HT₂ receptors antagonist prescribed in the treatment of schizophrenia and various other psychiatric illnesses. Even though olanzapine is widely used in psychiatry, its effects on the architecture of pancreas, liver and kidneys are little known. The histology of pancreas especially has never been studied. For these reasons, the current study was designed to elucidate the toxic effects of chronic administration of olanzapine on pancreas, liver and kidneys and the enzymes released by these tissues in an escalating dose manner. Methods: Fourteen male rats were divided into two groups equally, the olanzapine group and the controls. Olanzapine was administered in a dose of 5 mg/kg/d for the first eight weeks, 10 mg/kg/d for next four weeks and 15 mg/kg/d through the last two week period of 14 weeks experiment. The controls received acidified saline only. Both the groups received restricted diet (20 g/12 h). The body weight and level of random blood sugar (RBS) were measured on a weekly basis. The levels of lipase, amylase, alanine transaminase (ALT) and aspartate transaminase (AST) were determined terminally. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Results: Significant loss in body weight, change in the level of random blood sugar (^∗∗P < 0.05, ^∗∗∗P < 0.001) and significant rise in amylase and lipase levels (^∗P < 0.05, ^∗∗∗P < 0.001) were observed. However, the same treatment has shown no significant change in the levels of alanine and aspartate transaminases (P > 0.05). The pancreas has shown derangement of beta cells and fibrotic growth. A mild to moderate focal increase in glomerular cellularity, cellular proliferation and glomerular capsules with negligible basement membranes were observed in the kidneys. No changes were observed in the architecture of the liver. Conclusion: The findings of this study indicated that the incidence of adverse effects associated with olanzapine could be prevented/alleviated/delayed by allowing restricted diet.