Chronic treatment with pioglitazone exerts a more prominent gastroprotective effect on the stomach ulcers of cirrhotic rats compared to control group probably due to constitutive nitric oxide synthase induction or inducible nitric oxide synthase inhibition. Suppression of IL-1β could be another mechanism in pioglitazone-induced healing effect of gastric ulcers in cirrhotic rats.

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Objectives:The study aimed at examining the role of oxidative stress in cadioprotective effects of oleuropein in a rat model of simultaneous type 2 diabetes and renal hypertension.Materials and Methods:Five groups of male Sprague-Dawley rats including a control group, a diabetic-hypertensive group receiving vehicle, and three diabetic-hypertensive groups receiving oleuropein at 20, 40, or 60 mg/kg/day were used. Blood pressure and glucose, serum malondialdehyde, and erythrocyte superoxide dismutase were measured, and animal's hearts with ischemia/reperfusion injuries were used using Langendorff technique.Results:Blood pressure, blood glucose, serum malondialdehyde, infarct size, coronary effluent creatine kinase-MB, and coronary resistance of diabetic-hypertensive group were significantly higher than those of the control group, while those of the oleuropein-receiving groups were significantly lower than those of the diabetic hypertensive group receiving the vehicle. Erythrocyte superoxide dismutase, left ventricular developed pressure, and rate of rise and rate of decrease of ventricular pressure of diabetic-hypertensive group were significantly lower than those of the control group. These parameters as well as heart rate of oleuropein-receiving groups were significantly higher than those of the diabetic-hypertensive group.Conclusion:The findings indicate that oleuropein offered cardioprotection, which might be partly mediated by its antioxidant properties.

Oleuropein mediates most of the beneficial effects of olive products. This study examined the role of oxidative stress in the effects of oleuropein on lipid profile and blood glucose in rats with simultaneous renovascular hypertension and type 2 diabetes. Eight groups (n = 7-9 each) of male Sprague-Dawley rats including a control, a type 2 diabetic, a renovascular hypertensive, a sham, a simultaneously hypertensive diabetic receiving vehicle, and 3 simultaneously hypertensive-diabetic receiving 20, 40, or 60 mg/kg/day oleuropein were used. Four weeks after treatment, blood glucose, lipid profile, and biomarkers of oxidative stress were measured, and glucose tolerance test (GTT) was performed. Simultaneously hypertensive diabetic rats had significantly higher blood pressure, blood glucose, and serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and malondialdehyde. They also had lower serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and impaired glucose tolerance. Oleuropein significantly reduced blood pressure, blood glucose, and serum total cholesterol, LDL-C, triglyceride and malondoaldehyde. It also increased serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and improved glucose tolerance. The findings show that the model is associated with impaired glucose tolerance, and adverse lipid profile. They also show that oleuropein, partly by an antioxidant mechanism, improves glucose tolerance and changed lipid profile favorably.

The mechanism of oleuropein's antihypertensive effects was examined in rat model of simultaneous type 2 diabetes and renal hypertension (diabetic hypertensive). Five groups of male Sprague-Dawley rats including a control, a diabetic-hypertensive group receiving vehicle, and three diabetic-hypertensive groups receiving oleuropein at 20, 40, or 60 mg/kg/day were used. The duration of diabetes was 10 weeks; during the last 4 weeks of which, animals were hypertensive and received vehicle or oleuropein. Systolic blood pressure, glucose and malondialdehyde, heart rate, and maximal response to phenylephrine (PE) in the absence of nitro-L-arginine methyl ester (L-NAME) of oleuropein-treated groups were significantly lower than those of vehicle-treated group. Erythrocyte superoxide dismutase, maximal response to PE in the presence of L-NAME, and maximal response to acetylcholine (Ach) of oleuropein-treated groups were significantly higher than those of vehicle-treated group. The findings indicate that antihypertensive effects of oleuropein might be partly mediated by improving the release of nitric oxide, and antioxidant and sympathoplegic activities.