Long-term treatment of diabetic rats with vanadyl sulfate or insulin attenuate acute focal cerebral ischemia/reperfusion injury via their antiglycemic effect

Abstract

It is well-known that patients with diabetes mellitus have worse clinical outcomes following acute ischemic stroke. The intensifying effects of diabetes on ischemic brain injury have been shown to be mostly due to hyperglycemia, rather than the lack of insulin direct effects on brain. It is also well-approved that vanadium compounds have insulin-like and anti-diabetic effects, and the present study was designed to compare the protective effects of diabetes treatment with vanadium or insulin on ischemic/reperfused brain injury. Male Sprague-Dawley rats were divided into 4 groups (n = 21). Two groups of streptozotocin-induced diabetic rats were treated with either vanadyl sulfate or insulin at proper doses to similarly attenuate hyperglycemia during 45 days, while there was no treatment in the control diabetic and non-diabetic sham groups. Thereafter, all treated and non-treated diabetic rats were subjected to 60-min of the right middle cerebral artery occlusion followed by 12-h reperfusion, and then their brains were removed for evaluating blood-brain barrier leakage, tissue swelling, infarct size and oxidant status in both hemispheres. Vanadium and insulin that equally reduced blood glucose and water intake had some differences in their antidiabetic effects of ameliorating weight loss and hypertension during 45-days treatment period. However, they caused similar decrements in levels of Evans blue dye extravastion, edema, infarct volume and malondialdehyde in ischemic/reperfused cerebral hemisphere. Therefore, it can be suggested that insulin and vanadium via their antiglycemic effect cause reduction in cerebral production of oxidants following acute focal ischemia/reperfusion, which attenuate BBB disruption and brain tissue injury.

RETRACTED: Rapamycin Pretreatment Alleviates Cerebral Ischemia/Reperfusion Injury in Dose-Response Manner Through Inhibition of the Autophagy and NFκB Pathways in Rats

“…Stroke is accepted as the second leading cause of death in adults worldwide, which is characterized by cerebral ischemia because of disturbances for cerebral blood flow caused by thrombi or emboli. 1 - 3 Despite advances in the treatment technique, the prognosis of stroke remains poor. Till date, very limited medications such as tissue plasminogen activator are used to treat ischemic stroke.…”

Vanadyl Sulfate Effects on Systemic Profiles of Metabolic Syndrome in Old Rats with Fructose-Induced Obesity

“…Several studies have shown the insulin-mimetic effects of VS, and its hypoglycemic effect is the most investigated currently [18, 21, 23, 46]. In fact, our results are similar, old obese rats treated with VS-diminished glucose and insulin blood levels compared to respective control groups.…”

“…It has been evidenced that VS treatment of T2DM patients reduces serum cholesterol, triglycerides, and glucose [21, 25, 46]. In our study, total cholesterol and triglycerides decreased in treated aged rats but differences in other parameters, such as HDL and LDL, were not significant ( P > 0.05).…”

Potential of Selected Trace Elements in Patients with Diabetes Mellitus

“…The difference in effect can be explained by the fact that vanadyl is an active intracellular form of vanadium, while metavanadate is an extracellular form. However, in another study, the supplementation to obese patients of vanadyl sulfate, 50 mg two times per day, did not change insulin sensitivity (5,23). The optimal dose of vanadium is important because error in the dose volume of vanadium was toxic in experimental animals (22).…”