Evaluating the effects of insulin, metformin and glibenclamide on the pups’ prefrontal cortex and oxidative stress markers of streptozotocin-induced diabetic pregnant rats

Abstract

There is an upsurge in gestational diabetes mellitus with many devastating consequences for the mother and developing fetus. Insulin  therapy remains a mainstay. However, insulin is expensive and comes with the pain of multiple injections. Therefore, there is a need to  explore commonly administered oral hypoglycemic agents to cater for the increasing gestational diabetes mellitus-associated  neurological complications. This study assesses the effects of glibenclamide, metformin and insulin on the pups’ prefrontal cortex in  diabetic pregnant rats. 35 sexually matured adult female rats weighing between 120 g and 160 g were used and assigned into five groups (A to E) of seven rats each group. Diabetes was induced by streptozotocin (45 mg/kg and 35 mg/kg; ip). Hyperglycemic rats were treated  with insulin (1.0 UI daily), metformin (200 mg/kg/day) and glibenclamide (0.6 mg/kg/day). Body weight and blood glucose levels were  evaluated. Rats were sacrificed at 18-day gestation, the pups were harvested, and their brains were processed for tissue oxidative stress  markers and various histological examinations. Glibenclamide and metformin caused a significant blood glucose reduction at 37.9% and  40.7%, respectively, compared to the insulin group (33.09%). There was no significant difference in the body-organ ratio in rats treated  with metformin when compared to rats treated with insulin. Metformin and glibenclamide had a significant increase in tissue glutathione  reductase and a decrease in malondialdehyde compared with insulin and diabetic control groups. The pups’ prefrontal cortex showed  degenerated neuronal cells in the diabetic control animals. The diabetic rats treated with metformin and glibenclamide showed improved  pyramidal neurons compared with diabetic and insulin groups. This study suggests that metformin and glibenclamide  glycemic control may prevent and improve antioxidant enzymes and reverse some neurotoxic effects caused by streptozotocin-induced  diabetes in rats.