Protective effects of N(1)-2,4-dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato-oxovanadium (IV) on oxidative brain injury in streptozotocin-induced diabetic rats

Abstract

Diabetes is usually accompanied by increased production of free radicals or impaired antioxidant defenses. The brain is a target tissue of the oxidative attacks caused by diabetes, and there are observed changes in the biochemical parameters of this tissue in the hyperglycemic state. In this study, we aimed to show the effect of N(1)-2,4-dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato-oxovanadium (IV) (VOL) compound on diabetic damaged brain tissue, induced by streptozotocin (STZ) on 3.0-3.5-month-old male rats. Single dose of STZ at 65 mg/kg was used to make rats diabetic. Four groups were created randomly. Group (i): control (intact) animals; Group (ii): VOL given control animals; Group (iii): STZ-induced diabetic animals; and Group (iv): orally VOL administered STZ-induced diabetic rats. VOL (0.2 mM/kg/day) administration to control and diabetic animals was performed for a period of 12 days. At the end of day 12, the brain tissues were taken and homogenized. The clear supernatants were used for the determination of glutathione (GSH), lipid peroxidation (LPO), nonenzymatic glycosylation (NEG), and protein levels. Alanine and aspartate transaminases and acetylcholinesterase (AChE), myeloperoxidase (MPO), xanthine oxidase (XO), and oxidative stress marker enzymes activities were also estimated from the homogenates. According to the obtained results, there is found significant elevation of MDA and NEG levels and activities of transaminases, MPO and XO; whereas the GSH content and the activities of AChE and antioxidant enzymes were strongly decreased in the STZ-induced diabetic brain tissues in comparison to control group animals. Twelve days of administration of VOL complex to the diabetic animals reversed all biochemical parameters significantly in diabetic brain tissues. Our findings suggest that the VOL complex may be an ideal candidate to be used as an anti diabetic agent to improve oxidative injury and protect the brain tissue against damage caused by diabetes. This healing effect of the VOL complex may be due to its antioxidant activity and the insulin-mimetic effects of vanadium.