Modulatory Effect of Pioglitazone on Sperm Parameters and Oxidative Stress, Apoptotic and Inflammatory Biomarkers in Testes of Streptozotocin-Induced Diabetic Rats

Background and Aims: Diabetes mellitus causes testicular damage by increasing oxidative stress and inflammation. In the present study, modulation of oxidative stress by pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor-&gamma;, was examined in testis of streptozotocin-induced diabetic rats. Materials and Methods: Diabetes was induced by a single dose of streptozotocin (65 mg/kg, i.p.) injection in male Wistar rats. 32 adult male rats were divided into four groups (n=8): control, diabetic, diabetic pioglitazone (1 mg/kg/day) and diabetic pioglitazone (10 mg/kg/day). Rats were treated with pioglitazone for 5 weeks. Serum testosterone levels were estimated. Reproductive damage was evaluated by sperm parameters (viability, motility, morphology and count). Oxidative stress markers were evaluated in testicular homogenate. Pro-inflammatory cytokines (tumor necrosis factor-&alpha; and interleukin-1&beta;) levels, expressions of inflammatory (inducible nitric oxide synthase and nuclear factor-&kappa; B) and apoptotic markers (caspase-3) in testicular tissue were performed by enzyme-linked immunosorbent assay and western blot. Pioglitazone treatment significantly increased sperm parameters (p<0.05). No significant decrease in serum level of testosterone was observed in the pioglitazone treated mice (p>0.05). Aside from reducing the elevated tissue nitric oxide and malondialdehyde levels, pioglitazone increased the reduced superoxide dismutase, catalas and total antioxidant capacity in testes compared to diabetic rats (p<0.05). Pioglitazone reduced testicular inflammation by decreasing the expressions of inducible nitric oxide synthase, nuclear factor-&kappa;B and pro-inflammatory cytokines levels and inhibited cell death by decreasing the expressions of caspase-3 (p<0.05). Conclusions: Pioglitazone attenuated testicular damage in diabetic rats by decreasing oxidative stress, testicular inflammation and testicular damage.