Treatment of Alloxan-Induced Diabetic Rats with Metformin or Glitazones is Associated with Amelioration of Hyperglycaemia and Neuroprotection

Abstract

Neurobehavioural and cognitive impairments are reportedly associated with both types of diabetes mellitus; and the structural and molecular aberrations in support of these are emerging. In the present study, we report the effects of induced diabetes and its treatment with or without oral hypoglycaemic drugs on the morphology and oxidative stress status of the prefrontal cortex. Hyperglycaemia was induced in fasted Wistar rats with alloxan (150 mg/kg body weight). Hyperglycaemic rats were treated with or without oral hypoglycaemic drugs (metformin, 150 mg/kg/d; pioglitazone, 3 mg/kg/d; and rosiglitazone, 10 mg/kg/d). At 28 days of treatment, prefrontal morphology was studied by the cresyl fast violet (CFV) and luxol fast blue (LFB) techniques; and malondialdehyde (MDA) and superoxide dismutase (SOD) were assayed in prefrontal homogenate. Blood glucose was estimated by the glucose oxidase method. Prefrontal cortex neurons showed weak affinity for CFV and LFB in the untreated diabetic rats; as opposed to the relatively strong affinity for these stains in the non-diabetic control rats and diabetic rats on oral hypoglycaemic interventions. In the latter, blood glucose was not significantly different (P>0.05) from the control at 28 days of treatment. Moreover, prefrontal MDA and SOD were not significantly different between all the groups (P>0.05). These findings suggest that morphologic aberrations are provoked by untreated diabetes mellitus, even in the absence of oxidative stress; and that oral hypoglycaemic interventions are neuroprotective in alloxan-induced diabetic rats.