Related Experiment Video
Updated: May 27, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Role of Pioglitazone with Metformin or Glimepiride on Oxidative Stress-induced Nuclear Damage and Reproductive
Syed Imam Rabbani1, Kshama Devi, Salma Khanam
1Department of Pharmacology, Al-Ameen College Of Pharmacy, Opp. Lalbagh Main Gate, Hosur Road, Bangalore-560027, India.
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.
Insights
The combination of pioglitazone and metformin effectively reduced nuclear damage and sperm abnormalities in diabetic rats by improving antioxidant status. Pioglitazone with glimepiride showed no significant protective effects.
Area of Science:
- Endocrinology
- Toxicology
- Pharmacology
Background:
- Oxidative stress in diabetes contributes to secondary complications like cancer and birth defects.
- Effective management of blood glucose is crucial for preventing diabetic complications.
Purpose of the Study:
- To evaluate the protective effects of pioglitazone combined with metformin or glimepiride.
- To assess the impact on nuclear damage and reproductive toxicity in a type-2 diabetes rat model.
Main Methods:
- Rats were induced with type-2 diabetes using nicotinamide and streptozotocin.
- Combinations of pioglitazone with metformin or glimepiride were administered orally for 4 weeks.
- Evaluated micronuclei formation, sperm abnormalities, and antioxidant status (LPO, CAT, SOD).
Main Results:
- Pioglitazone plus metformin significantly reduced micronucleated erythrocytes and sperm defects.
- This combination also increased the P/N ratio and caudal sperm count.
- Pioglitazone plus glimepiride did not show significant protective effects against nuclear or sperm damage.
Conclusions:
- The pioglitazone-metformin combination demonstrates significant protective effects against nuclear damage and sperm abnormalities in diabetic rats.
- These benefits are attributed to enhanced antioxidant status.
- Pioglitazone-glimepiride combination was ineffective in mitigating these diabetic complications.
Related Concept Videos
Oral Hypoglycemic Agents: Biguanides and Glitazones
Dipeptidyl Peptidase 4 Inhibitors
Oral Hypoglycemic Agents: Glinides
