Progesterone and Cilostazol Protect Mice Pancreatic Islets from Oxidative Stress Induced by Hydrogen Peroxide

Reactive oxygen species and oxidative stress impair β-cell function and reduce insulin secretion. It has been shown that progesterone and cilostazol possess antioxidant properties. The present study was aimed to investigate in-vitro pretreatment effect of progesterone and cilostazol on insulin secretion as well as their protective effects against hydrogen peroxide-induced oxidative stress in pancreatic isolated islets from mouse. Pancreatic islets were isolated from 84 male NMRI mice (25-30 g) by collagenase digestion method and pretreated for 48 h with cilostazol (10 μM), progesterone (0.5 μM) and glibenclamide (10 μM) in culture medium. Then islets were exposed to hydrogen peroxide (H(2)O(2). 500 μM) for 2 h. Next, culture mediums containing glucose concentration of 2.8 mM or 16.7 mM were added to them and incubated in this status for 1 h. At the end, the rate of insulin output from islets, lipid peroxidation and antioxidant enzymes activities in islet tissues were assayed. Exposure of islets to H(2)O(2), resulted in a significant decrease in insulin secretion, superoxide dismutase and catalase activities (P < 0.001). Also islets malondialdehyde levels were increased by H(2)O(2), after addition of 2.8 mM (P < 0.05) and 16.7 mM (P < 0.001) glucose. 48 h pretreatment of islets with cilostazol and progesterone, significantly reverted back this changes (P < 0.05). Results of present study showed that cilostazol and progesterone protect mice pancreatic islets against H(2)O(2)-induced oxidative stress. At the end, our results suggested that protective effects of progesterone and cilostazol are mediated by augmentation the antioxidant defence system of islets.