Abstract
Uric acid, a potent antioxidant for humans, birds, reptiles, and some primate species, is the end-product of purine degradation that is formed in the xanthine/hypoxanthine reactions catalyzed by xanthine oxidase. Associated with the evolutionary loss of urate oxidase (the enzyme that oxidizes uric acid resulting in the formation of allantoin) and resulting increase in concentrations of uric acid is a prolonged life span. Uric acid is known to scavenge peroxynitrite and other free radicals that can cause an imbalance of oxidants leading to oxidative stress. Uric acid also has a role in protecting DNA from single-strand breaks caused by free radicals in the body leading to a protective effect in neurodegenerative diseases. The brain is particularly vulnerable to oxidative stress as it is considered an ‘expensive tissue’ with a particularly high metabolic rate and comparatively increased utilization of oxygen. Brain tissue is also high in unsaturated lipids, which makes it more susceptible to free radical damage. Oxidative stress is thus linked to the pathogenesis of neurodegenerative diseases and also ischemic brain injury. In this review, we summarize the function of uric acid in alleviating oxidative damage and providing protection to neural cells during injury and disease.
Highlights
Uric acid has been studied extensively in many physiological and pathological systems including cancer [1] due to its role as a potent plasma antioxidant that scavenges singlet oxygen, peroxy radicals, and hydroxyl radicals
Oxidative damage plays a role in the progression of neurodegenerative disease states and injury to neural tissue
The brain and central nervous system are exposed to oxidative damage generated by free radical processes throughout life
Summary
Uric acid has been studied extensively in many physiological and pathological systems including cancer [1] due to its role as a potent plasma antioxidant that scavenges singlet oxygen, peroxy radicals, and hydroxyl radicals. Free radical imbalance within a biological system can result in oxidative damage and inflammation which can, increase pathogenesis of disease. Reactive oxygen species (ROS) are fundamentally free radicals derived from molecular oxygen. Referred to as the triplet state, is considered to be a bi-radical, meaning that it contains two unpaired electrons in the outer shell. The two electrons exhibit the same spin which enables the oxygen molecule to react with one electron at a time. Oxygen is not reactive with the two electrons. If one of the unpaired electrons becomes excited it can alter its spin state, which results in a singlet oxygen species. The singlet oxygen can react with other pairs of electrons, especially those involved in double bonds, and can become a powerful oxidant [3]
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