Effect of Telmisartan on Olanzapine Induced Metabolic Syndrome in Ovariectomized Female Sprague-Dawley Rats

Vennam Pavani, Manonmani Alvin Jose, Shaik Mohammad, Duraiswami Sathyamurthy, Balasubramanian Nandha kumar

Abstract


Background: Menopause increases the prevalance of metabolic syndrome in women. Olanzapine is an atypical antipsychotic drug which is used in the treatment of psychiatric disorders, include schizophrenia and bipolar disorder. But it is associated with serious metabolic side-effects, include weight gain, hypertension, hyperlipidemia, hyperglycemia, glucose intolerance and insulin resistance which results in metabolic syndrome. The prevalence of metabolic syndrome is more in patients with schizophrenia compared to the general population. Telmisartan an antihypertensive agent, is an angiotensin II type-I receptor blocker (ARB) also activates peroxisome proliferator-activated receptor gamma (PPARy) and provide beneficial effects for glucose and lipid metabolism. Thus the objective of the present study was to evaluate the effect of telmisartan and additional influence of menopause status on olanzapine induced metabolic syndrome in female Sprague-Dawley rats.  

Methods: After four weeks of ovariectomy, olanzapine (5 mg/kg) was administered by oral route for 28 days to induce metabolic syndrome in female Sprague-Dawley rats. Thirty female Sparague-Dawley rats were randomly divided into five groups as normal control; ovariectomy control (OVX); ovariectomy + olanzapine control (OVX+OLZ); OVX + Telmisartan (5 mg/kg); OVX + OLZ + Telmisartan (5 mg/kg). After 28 days of treatment, the blood samples were collected and analyzed for blood glucose, plasma insulin, lipid profiles, SGOT, SGPT and body weights of all groups were recorded.  

Results: OVX control and OVX + OLZ control groups showed significant (P < 0.01) increase in body weight, blood glucose, plasma insulin, total cholesterol, triglycerides, LDL-C, VLDL-C, SGOT, SGPT and significant (P < 0.01) decrease in HDL-C when compared to normal control. While OVX group and OVX + OLZ group treated with telmisartan showed significant decrease in body weight gain (P < 0.05), blood glucose (P < 0.01), plasma insulin (P < 0.01), total cholesterol (P < 0.01), triglycerides (P < 0.05, P < 0.01), LDL-C (P < 0.01), VLDL-C (P < 0.05, P < 0.01), SGOT (P < 0.05, P < 0.01), SGPT (P < 0.01) and significant increase in HDL-C (P < 0.01) when compared to OVX control and OVX + OLZ control group. The results of histopathological studies provide strong support to our results. 

Conclusion: Telmisartan attenuate the development of metabolic syndrome induced by olanzapine in ovariectomized female Sprague-Dawley rats.




doi:10.4021/jem100w


Keywords


Menopause; Ovariectomy; Metabolic syndrome; Insulin resistance; Hyperlipidemia; Hyperglycemia; Peroxisome proliferator-activated receptor gamma (PPAR-gamma)

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