Research Article EVALUATION OF EFFECTS OF RUTIN ON OXIDATIVE STRESS IN DIABETIC RAT *S.K.BAIS 1 , S.G.SHRIRAO 2 , GAUTAM SHENDE 2 , N.I.KOCHAR 2 , AVINASH JIDDEWAR 3 , A.V.CHANDEWAR 2 1 Research Scholar, PRIST University.Thanjavur (TN) India, 2 Department of Pharmacology, P.W.College of Pharmacy, Yavatmal, India, 3 Received: 01 May 2012, Revised and Accepted: 15 Jun 2012 ABSTRACT Oxidative stress which usually results from excessive production of ROS and/or diminished activity of antioxidants have been implicated as a major contributor to the etiology of severe pathologies, including diabetes. Moreover, increasing evidence shows that excess ROS acts as negative regulators of insulin signaling leading to insulin resistance, a known metabolic abnormality associated with diabetes. Oxidative stress is currently suggested as a mechanism underlying diabetes and diabetic complications. Enhanced oxidative stress and changes in antioxidant capacity, observed in both clinical and experimental diabetes mellitus, are thought to be the etiology of chronic diabetic complications. In recent years, much attention has been focused on the role of oxidative stress, and it has been reported that oxidative stress may constitute the key and common event in the pathogenesis of secondary diabetic complications. We observed a significant increase in Superoxide dismutase (SOD) and Catalase activity with the exception, an increase in activity of LPO (Lipidperioxidase) as compared to the control subjects. Rutin improved SOD and Catalase activity in diabetic rat with gastropathy when compared with the normal rat treated with vehicle. NSPM, College of Pharmacy, Darwha, Dist Yavatmal, India. Email: sanjaybais@rediffmail.com Keywords: Diabetes, Rutin, SOD, LPO, Catalase INTRODUCTION Free radicals which are atomic or molecular chemical species with unpaired electrons are highly unstable and can react with other molecules by giving out or accepting single electron. Oxidation processes are one of the most important routes for producing free radicals in food, drugs and even living systems. These unstable molecules are capable of causing cellular damage, which leads to cell death and tissue injury. Free radicals are linked with the majority of human diseases like ageing, atherosclerosis, cancer, diabetes, liver cirrhosis, cardiovascular disorders, etc. 1 Oxidative stress which usually results from excessive production of ROS and/or diminished activity of antioxidants have been implicated as a major contributor to the etiology of severe pathologies, including diabetes. Moreover, increasing evidence shows that excess ROS acts as negative regulators of insulin signaling leading to insulin resistance, a known metabolic abnormality associated with diabetes. 2 Free radicals may play an important role in the causation and complications of diabetes mellitus. In diabetes mellitus, alterations in the endogenous free radical scavenging defense mechanisms may lead to ineffective scavenging of reactive oxygen species, resulting in oxidative damage and tissue injury. 3, 4 Oxidative stress is currently suggested as mechanism underlying diabetes and diabetic complications. Enhanced oxidative stress and changes in antioxidant capacity, observed in both clinical and experimental diabetes mellitus, are thought to be the etiology of chronic diabetic complications. In recent years, much attention has been focused on the role of oxidative stress, and it has been reported that oxidative stress may constitute the key and common event in the pathogenesis of secondary diabetic complications. Free radicals are continually produced in the body as a result of normal metabolic processes and interaction with environmental stimuli. Oxidative stress results from an imbalance between radical-generating and radical-scavenging systems, i.e. increased free radical production or reduced activity of antioxidant defenses or both. Implication of oxidative stress in the pathogenesis of diabetes is suggested, not only by oxygen free-radical generation, but also due to nonenzymatic protein glycosylation, auto-oxidation of glucose , impaired glutathione metabolism, alteration in antioxidant enzymes , lipid peroxides formation and decreased ascorbic acid levels . In addition to GSH, there are other defense mechanisms against free radicals like the enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) whose activities contribute to eliminate superoxide, hydrogen peroxide and hydroxyl radicals. 5, 6, 7 Biomarkers of oxidative stress: in vivo Diabetes studies Lipid Peroxidation Hydroperoxides have toxic effects on cells both directly and through degradation to highly toxic hydroxyl radicals. They may also react with transition metals like iron or copper to form stable aldehydes such as malondialdehydes that will damage cell membranes. Peroxyl radicals can remove hydrogen from lipids, producing hydroperoxides that further propagate the free-radical pathway. The damage caused by LPO, is highly detrimental to the functioning of the cell 8 Glutathione Levels Reduced glutathione is a major intracellular redox buffer that may approach concentrations up to 10 mM. Glutathione functions as a direct free-radical scavenger, as a co substrate for glutathione peroxidase activity, and as a cofactor for many enzymes, and forms conjugates in endo- and xenobiotic reactions. 9 Catalase Catalase, located in peroxisomes, decomposes hydrogen peroxide to water and oxygen. Documented changes in catalase activity in chemically induced diabetic animals. For example, catalase activity is consistently found to be elevated in heart and aorta, as well as brain of diabetic rats. In contrast to decreased renal, hepatic and red blood cell catalase activity, catalase activity in liver and kidney of diabetic animals is increased. 10 Superoxide Dismutase (SOD) Isoforms of SOD are variously located within the cell. CuZn-SOD is found in both the cytoplasm and the nucleus. Mn-SOD is confined to the mitochondria, but can be released into extracellular space. SOD converts superoxide anion radicals produced in the body to hydrogen peroxide, thereby reducing the likelihood of superoxide anion interacting with nitric oxide to form reactive peroxynitrite Latent autoimmune diabetes of adults (LADA) is a condition in which Type 1 diabetes develops in adults. Adults with LADA are frequently initially misdiagnosed as having Type 2 diabetes, based on age rather than etiology. Pre-diabetes indicates a condition that occurs when a person's blood glucose levels are higher than normal but not high enough for a diagnosis of type 2 diabetes. Many people destined to develop type 2 diabetes spend many years in a state of pre-diabetes which has been termed "America's largest healthcare epidemic. 11 Diabetes is characterized by immune system dysregulation and oxidative stress 12 This International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 4, Suppl 5, 2012 A A c c a a d d e e m mi i c c S Sc c i i e e n n c c e e s s