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

Abstract

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 nondiabetic 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 STZinjection, 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.

In Vivo Assessment of Antioxidants and Antihyperglycemic Effect of Barleria cristata leaves in Streptozotocin- Induced Diabetic Rats

“…Recycling of tocopheroxyl radicals to tocopherol is achieved with ascorbic acid (Lobo et al, 2010). In our study, ascorbic acid was decreased in diabetic rats as reported earlier (Iwata et al, 2010). Reduction in liver and kidney ascorbic acid levels may occur due to excessive oxidation and lack of regeneration from their radical form to reduced form.…”

Protective Effect of Chlorella vulgaris against Lead-Induced Oxidative Stress in Rat Brains

“…The protective role of antioxidant such as α-tocopherol, ascorbic acid and methionine is reducing the lipid peroxidation as evidenced by a decreased MDA concentration in the brain because of Pb-induced oxidative stress. 27) Taking these findings together, it is suggested that oxidative stress, which is induced by lead, is recovered by natural antioxidants, such as ascorbic acid, 28) epigallocatechin-3-gallate 29) and plant extracts etc. 30,31) Marine algae have the potential to improve the biochemical imbalances induced by various toxins associated with free radicals.…”

Diabetes-Mediated Exacerbation of Neuronal Damage and Inflammation After Cerebral Ischemia in Rat: Protective Effects of Water-Soluble Extract from Culture Medium of Ganoderma lucidum Mycelia

“…Impairment of these antioxidant enzymes caused by nonenzymatic glycation is responsible for the increase of lipid peroxidation in the brain of diabetic animals. In a previous study, we also observed that the level of lipid peroxidation marker TBARS (thiobarbituric acid reactive substances) was elevated and activity of SOD, CAT and GPx was decreased in STZ-induced diabetic rat brain, which were reversed by chronic treatment of ascorbic acid (Iwata et al, 2010). Thus, the enhanced oxidative stress in diabetes is considered to cause functional impairment of antioxidant enzymes and the resulting diminution in antioxidative defense leads to further enhancement of radical reactions and other dysfunctions in the brain.…”

“…Focal cerebral ischemia was induced by MCAO with a standard intraluminal filament technique as previously described (Iwata et al, 2010). The animals were anesthetized with 4% halothane and maintained with 1.5% halothane and 30% oxygen under spontaneous respiration.…”