ABSTRACT
Diabetes mellitus is a group of metabolic diseases caused by a combination of insulin resistance and impaired insulin secretion by pancreatic β cell. Long-lasting effect of hyperglycemia results in increased oxidative stress. Oxidative stress results from an imbalance between radical generating and radical scavenging systems. Increased oxidative stress has been shown to be increased in both insulin-dependent (IDDM), and noninsulin-dependent (NIDDM) diabetes mellitus and it could cause initial β cell damage in type I diabetes, or impaired insulin production, release or function in type II diabetes. Therefore, people with diabetes may also have greater antioxidant requirements because of increased production of free radicals in hyperglycaemia. This present study was designed to evaluate the histological effects and antioxidant enzyme activities of metformin and vitamin E combination therapy on pancreas, liver, and kidney in streptozotocin-induced diabetic albino rats.
Male albino rats weighing (200-300 g) were fasted overnight and diabetes mellitus was induced by a single dose (45 mg/kg body weight) intraperitoneal injection of streptozotocin. After 48 hours diabetes mellitus was confirmed (blood sugar ≥ 200 mg/dl) and the animals were grouped into five groups of five rats each that included non-diabetic control rats with no drug treatment, untreated diabetic rats and diabetic rats that received different treatments orally once daily. Blood glucose levels were recorded weekly. After two weeks treatment, animals were sacrificed under chloroform anaesthesia and their kidneys, livers, and pancreas were harvested and histologically processed and stained using H & E. Statistical analysis was done using one-way analysis of variance followed by Dunnett’s post-hoc test of multiple comparison (Graphpad Prism® 6, San Diego, USA). P-value was set at P < 0.05 for significant difference.
The results of the study showed that metformin (500 mg/kg), vitamin E (600 mg/kg), and metformin and vitamin E combination significantly reduced the mean blood glucose levels. Metformin alone caused a greater reduction in the mean blood glucose level than vitamin E and metformin and vitamin E combination. In the histological studies, metformin and vitamin E combination showed a greater regeneration of the pancreatic islet cells. This study has demonstrated that the addition of vitamin E (an antioxidant) as an adjunct to metformin has a better enhancement on blood glucose lowering effect in the management of type 2 diabetes mellitus and also seems to have a synergistic effect in protecting B-cells of pancreas from the STZ induced oxidative stress and damage.
