Protective Effects of Oral Administrated Ascorbic Acid against Oxidative Stress and Neuronal Damage after Cerebral Ischemia/Reperfusion in Diabetic Rats

Diabetes enhances oxidative stress and exacerbates acute ischemic injury. Previous studies have demonstrated that infarct volumes were greater in diabetic animals caused by a transient cerebral ischemia as compared with non-diabetic animals. Ascorbic acid (AA) as a naturally occurring major antioxidant is reported to be low in diabetic tissues. Therefore, we examined the effects of daily supplementation of AA on lipid peroxidation and the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in streptozotocin (STZ)-induced diabetic rat brain. Additionally, we also investigated whether AA improves the exacerbation of neuronal damage induced by middle cerebral artery occlusion followed by reperfusion (MCAO/Re) in diabetic state. Type1-diabetes was induced in male Sprague Dawley rats by STZ (60 mg/kg of intraperitoneal injection). Five weeks after STZ-injection, the diabetic rats showed enhanced lipid peroxidation and impaired activity of antioxidant enzymes in the brain. Furthermore, the gene expression of glucose transporter GLUT1, which locates in the endothelial cells of the blood-brain-barrier and transports oxidized AA as the main source of AA supply to the brain, was downregulated in the diabetic brain. AA-supplemented (100 mg/kg daily, 2 weeks) diabetic rats showed normal levels of all these parameters. A diabetic state markedly aggravated MCAO/Re-induced neurological deficits and cerebral injury assessed by infarction volume. Treatment of AA remarkably improved both parameters in the diabetic rats. These results suggest that daily intake of AA relieves the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to improvement of augmented oxidative stress.