sara khosraviani

Diabetes is one of the most prevalent endocrine disorders in humans, and its first-line medication is metformin. Peroxisome proliferator-activated receptor gamma (PPAR–γ) agonists are the adjuncts to metformin. Bavachinin is a PPAR pan-agonist with fewer side effects than metformin" into PPAR–γ agonists. In this study, the synergistic effects of metformin and Bavachinin were investigated on type II diabetic rats.

After four weeks of a high fat and glucose diet, type II diabetes was induced in 28 male Wistar rats, using injection of streptozotocin and nicotinamide. The animals were distributed into five groups of seven each: 1) Normal control (N), 2) Diabetic control (D), 3) Diabetic rats receiving metformin (DM), 4) Bavachinin (DB), and 5) Metformin plus Bavachinin (DMB). Oral glucose tolerance test (OGTT), fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of β-cell function (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR), and insulin sensitivity index (ISI) were obtained.

The OGTT results in DM, DB, and DMB groups were significantly improved compared to that of D group. The FBG levels were significantly lower in DMB than in DB, DM, and D groups. The FINS levels of DMB were significantly less than those of DB, DM, and D groups. The HOMA-IR and HOMA-β were comparable between DMB and N groups. The ISI improved significantly in DMB compared to those in DM, DB, and D groups.

Bavachinin may be used combined with metformin for the treatment of type II diabetes at lower doses of metformin, thus having fewer side effects.

Epilepsy is a neurological disorder caused by uncontrollable discharge of action potentials from neurons in the brain. After a seizure, oxidative stress may cause a significant neuronal damage. In the current study, we assessed the anticonvulsant and antioxidant properties of pioglitazone, a peroxisome proliferated activated receptor-γ (PPAR-γ) agonist that is used in type-2 diabetes, on pilocarpine-induced seizure in mice. 

Pilocarpine (400 mg/kg) or normal saline was injected intraperitoneally 4 hours after oral administration of Pioglitazone (80 mg/kg). Also, carboxymethyl cellulose was administered orally in control and Pilocarpine groups. After the administration of Pilocarpine all of the mice were observed for 1 hour to measure the seizure latency time. Pilocarpine-induced seizures were categorized using the Racine scale. Then all animals were decapitated, brain was removed and hippocampus was dissected. Finally, the level of Malondialdehyde (MDA) and Catalase (CAT) activity, Superoxide Dismutase (SOD), and Glutathione Reductase (GR) levels were quantified in hippocampus by biochemical methods.

Pioglitazone significantly increased the latency to seizure onset of stages 1-4 (P≤0.01-0.001). Also, pioglitazone prevented the development of stage 5 of the pilocarpine-induced seizure. After the seizure, pioglitazone significantly decreased the level of MDA (P<0.01) and elevated the levels of CAT (P<0.01), SOD (P<0.01) and GR (P<0.001) enzymes in the mice hippocampus compared to those in the pilocarpine group.

The findings of this study indicate that the antioxidant effect of pioglitazone may play an important role in its protective effects against neuronal damage caused by pilocarpine-induced seizure.