Preventive effect of pioglitazone on reproductive damage by suppression of testicular nitric oxide (NO) level in streptozotocin-induced diabetic rats

Background: It has been shown that diabetes mellitus has adverse effects on the male sexual and reproductive functions. Enhanced oxidative stress and changes in antioxidant capacity have important roles in the pathogenesis of chronic diabetes mellitus. Previous studies have demonstrated that pioglitazone is a potent inhibitor of inflammatory and potent antioxidants. The purpose of this study was to investigate the preventive effects of pioglitazone on nitric oxide (NO) levels of testicular tissues.Methods: Induction of experimental diabetes was done using single intraperitoneal injection of Streptozotocin (STZ) (Sigma, Germany) dissolved in citrate buffer (pH 4.5) at the dose of 65 mg/kg to overnight fasted rats. Only rats with blood glucose concentrations above 250 mg/dL were considered as diabetic. Animals were randomly divided into four groups of eight rats: control group, STZ-induced diabetic group (diabetic group) and STZ-induced diabetic groups treated with low or high doses of pioglitazone (Sigma, Germany) of 1 or 10(mg/kg/day, orally) for 5 weeks. Animals were euthanized on day 35 and one testis was homogenized in ice-cold Tris-HCL buffer (150 mM, pH 7.4). Testicular nitric oxide (NO) level was measured as total nitrite/nitrate, the stable degradation products of NO, by reduction of nitrate into nitrite using copperized cadmium, followed by color development with Griess reagent in acidic medium. Result: STZ caused marked increase (P < 0.05) in testicular NO levels compared with control group of rats. Administration of pioglitazone to diabetic rats, in low and high dosage, ameliorated abnormalities in testicular NO levels when compared with those in diabetic control group (p< 0.05).Conclusion: In conclusion, these findings indicate that pioglitazone may have a therapeutic effect against the autoimmune destruction of the testicular damage during the development of streptozotocin induced type 1 diabetes in rats.

کلیدواژه ها:

Nitric oxide ، Pioglitazone ، Type 1 diabetes