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.

Amelioration of thyroid dysfunction by magnesium in experimental diabetes may also prevent diabetes-induced renal impairment

“…Magnesium supplementation in this study, either alone or in combination with metformin, exerted a hypoglycemic effect, as did metformin in diabetic treated animals, which for magnesium may be ascribed to its documented potentiation of insulin secretory activities, its glucose regulatory and blood glucose stabilizing effects [7, 22]. Similarly the effects of Metformin, the most frequently prescribed first line therapy for individuals with type 2 diabetes [23], seen in this study may be linked to its ability to increase insulin mediated glucose utilization in peripheral tissues (such as muscle and liver) and thus improve glycemic control [24].…”

Prevention and treatment of brain damage in streptozotocin induced diabetic rats with Metformin, Nigella sativa, Zingiber officinale, and Punica granatum

“…Treatment with different substances containing antioxidants prevented the harmful effects of diabetes mellitus on neurological tissues. In the previous studies [38][39][40] , it has been found that metformin prevents the brain damage by reducing oxidative stress. The results of our study are in line with these studies, and significant prevention of the neuronal tissue damage was found in all areas of the brain of the animals.…”

Design and Synthesis of Pyrazole-3-one Derivatives as Hypoglycaemic Agents

“…During this period, animals in all groups had free access to standard diet and water. The blood was withdrawn by retroorbital plexus method [ 22 ]. On the same day, the blood glucose levels were estimated by using glucometer (Johnson & Johnson Pvt.…”