Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a polyphenolic phytoalexin that exerts cardioprotective, neuroprotective, and antioxidant effects. Recently it has been shown that obesity is associated with an increase in cerebral oxidative stress levels, which may enhance neurodegeneration. The present study evaluates the neuroprotective action of resveratrol in brain of obese (ob/ob) mice. Resveratrol was administered orally at the dose of 25？mg？kg？1 body weight daily for three weeks to lean and obese mice. Resveratrol had no effect on body weight or blood glucose levels in obese mice. Lipid peroxides were significantly increased in brain of obese mice. The enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and nonenzymatic antioxidants tocopherol, ascorbic acid, and glutathione were decreased in obese mice brain. Administration of resveratrol decreased lipid peroxide levels and upregulated the antioxidant activities in obese mice brain. Our findings indicate a neuroprotective effect of resveratrol by preventing oxidative damage in brain tissue of obese mice. 1. Introduction Obesity is a major risk factor for the development of type 2 diabetes. Roughly 30 percent of obese people are diabetic, and 85 percent of diabetics are obese. Other obesity-related conditions include heart disease, stroke, and certain types of cancer. According to the National Institutes of Health around 97 million Americans are affected by these conditions which is the second leading cause of death. Recently obesity has been shown to increase the level of cerebrocortical reactive oxygen species and impair brain function [1], suggesting that obesity may increase the risk for neurodegenerative conditions such as Alzheimer’s disease [2, 3]. Oxidative stress is associated with an increase in oxidizing species that destructs the vascular and neuronal cells in central nervous system. Oxidative stress is due to the imbalance between the oxygen free radicals generated and the antioxidant defense system to detoxify the reactive intermediates [4]. Oxidative stress changes the signaling pathways that may induce cellular responses such as inflammation, cell proliferation, and cell survival and death [5]. Reactive oxygen species (ROS) are chemically reactive molecules that consist of oxygen ions and peroxides that include hydrogen peroxide, singlet oxygen, nitric oxide, peroxynitrite, and superoxide free radicals. The release of peroxides and free radicals is toxic to the cell, which may lead to cell death.
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