Pioglitazone, a ppar-gamma ligand inhibited the nicotinamide streptozotocin induced sperm abnormalities in type-2 diabetic wistar rats

Oxidative stress due to chronic hyperglycemia is known to cause infertility in diabetic patients. Pioglitazone [PIO], a PPAR-gamma ligand is known to possess the antioxidant property however, its role on the oxidative stress mediated germinal damage in Type-2 diabetes mellitus [T2DM] is poorly studies in the literature. In this study, the effect of PIO [1 and 10 mg/kg, p.o. daily for 4 weeks] was evaluated against the nicotinamide [NA-230 mg/kg, ip] and streptozotocin [STZ-65 mg/kg, ip] induced changes in sperm abnormality and antioxidant status in Wistar rats. The effect of PIO on the male reproductive cells was studied by determining the sperm shape abnormality and sperm count in the experimental T2DM. The antioxidant profile was studied by estimating the serum lipid peroxidation [LPO], glutathione [GSH] and glutathione peroxidase [GPx] levels. The higher dose of PIO [10 mg/kg] significantly [P<0.001] reduced the sperm shape abnormality and increased the sperm count [P<0.00l], besides decreasing [P<0.05] the LPO and enhancing the GSH and GPx levels in the diabetic rats. However, the lower dose of PIO [1 mg/kg] produced inhibitory [P<0.05] effect against the changes induced by T2DM in the sperm shape abnormality and GSH levels. alpha tocopherol tested as alpha standard antioxidant agent prevented [P<0.001] the NA-STZ mediated alterations in sperm abnormalities and antioxidant enzyme levels. The results suggest that the inhibitory effect of PIO against the 12DM induced sperm abnormality could be related to its antioxidant property

Role of Pioglitazone with Metformin or Glimepiride on Oxidative Stress-induced Nuclear Damage and Reproductive Toxicity in Diabetic Rats

Background: Oxidative stress due to improper control of blood glucose in chronic diabetes plays a major role in the development of secondary complications including cancer and birth defect. The aim of this study is to evaluate the protective effect of combination of pioglitazone with metformin or glimepiride against the experimental type-2 diabetes induced nuclear damage and reproductive toxicity in rats. Methods: The combinations of Pioglitazone (Pio-1 mg/kg) with metformin (Met-50 mg/kg) or glimepiride (Gmp-0.2 mg/kg) given orally daily for 4 weeks were tested against nicotinamide (NA- 230 mg/kg, ip)-streptozotocin (STZ-65 mg/kg, ip)-induced micronuclei (MN) formation and sperm abnormalities in male Wistar rats. The antioxidant status was evaluated by measuring the levels of serum lipid peroxidation (LPO), catalase (CAT) and superoxide dismutase (SOD). Results: The administration of Pio+Met significantly (P<0.01) reduced the number of micronucleated erythrocytes, increased the polychromatic: normochromatic erythrocytes (P/N ratio), reduced (P<0.001) sperm morphology defects and increased (P<0.05) the caudal sperm count compared to the untreated diabetic condition. Furthermore, the Pio+Met combination enhanced the antioxidant status in diabetic animals. However, Pio+Gmp did not attenuate the nuclear and sperm defects or oxidative stress. Conclusions: The observations suggest that Pio+Met combination reduced nuclear damage and sperm abnormalities by enhancing the antioxidant status in the diabetic animals.