Syed Imam Rabbani

Protective role of glibenclamide against nicotinamide-streptozotocin induced nuclear damage in diabetic Wistar rats

Objective: To evaluate the protective effect of glibenclamide against the experimental diabetes-induced nuclear damage in Wistar rats. Materials and Methods: The anti-mutagenic effect of glibenclamide (0.5, 5 and 50 mg/kg, p.o daily for 4 weeks) was evaluated against the nicotinamide (NA)-streptozotocin (STZ) induced type-2 diabetes mellitus using bone marrow micronucleus and sperm abnormalities tests. The antioxidant status was tested by estimating the serum levels of lipid peroxidation (LPO), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Results: The results indicated that glibenclamide at 50 mg/kg decreased the frequency of micronuclei in erythrocytes (P < 0.05) and sperm shape abnormality (P < 0.01) besides enhancing the antioxidant status (P < 0.05) in the diabetic rats. However, glibenclamide treatment did not enhance the polychromatic and normochromatic erythrocytes (P/N) ratio and sperm count in the diabetic condition. Conclusion: The observations indicate that the glibenclamide has anti-mutagenic potential which could be related to the antioxidant effect and might also possess anti-proliferative property.

Effect of Thiazolidinediones on the Erythropoeitic and Germinal Cells in the Male Wistar Rats

Hyperglycemia is the main determinant of long term diabetic complications mainly through induction of oxidative stress responsible for secondary defects including cancer, infertility etc. Thiazolidinediones (TZDs) are known to posses the antioxidant potential against the reactive oxygen species. The ability of clinically used TZDs like Rosiglitazone (RSG) and Pioglitazone (PIO) in diabetic complications is still need to be studied extensively in the literature. In this study, the role of RSG and PIO on the frequency of nuclear and germinal cell damage was studied using bone marrow micronucleus (MN) test, sperm shape abnormality and sperm count in normal animals. The drugs were tested in the three doses (1, 10 and 100 mg/kg) after acute (48 hrs and 72 hrs) and chronic (4 weeks) treatment. The results indicated that RSG has produced significant (p < 0.01) decrease in P/N (polychromatic and normochromatic erythrocytes) ratio at 10 and 100 mg/kg without affecting the frequency of micronucleated erythrocytes, sperm shape morphology and sperm count. PIO in the tested doses did not induce any change in P/N ratio and sperm count but the higher dose (100 mg/kg) showed suppression of MN in normochromatic erythrocytes and % sperm shape abnormality compared to the control group.

Failure to detect the anti-mutagenic effect of insulin in experimental type-2 diabetic rats

Background: The oxidative stress is known to cause mutation-related disorders in diabetic patients. Materials and Methods: The present study was designed to investigate the anti-mutagenic effect of insulin in nicotinamide (NA: 230 mg/kg, i.p.) and streptozotocin (STZ: 65 mg/kg, i.p.) induced nuclear defects. Bone marrow micronucleus (MN) test and caudal epididymal sperm abnormalities were detected to find the somatic and germinal cell mutations, respectively. The antioxidant status was determined by estimating serum lipid peroxidation, catalase, superoxide dismutase and glutathione peroxidase levels. Results: The experimental type diabetes significantly (P < 0.001) reduced the antioxidant status and enhanced MN frequency and sperm defects compared to control animals. Although administration of insulin (1, 3, 5 and 7 IU/kg, s.c. for 4 weeks) significantly (P < 0.001) reduced hyperglycemia, it did not alter the antioxidant status, and somatic and germinal cell defects in diabetic rats. Conclusion: The results suggest that insulin did not have protective effect against the genotoxicity induced by NA-STZ diabetes.