Urate's Pro-Oxidant Effects

toxicity. So antioxidants can really help and slow the aging process, it can help protect

Main compounds of the enzymatic antioxidant system are three, namely, SOD, CAT and tT which have an important role in detoxifying of H2O2 and superoxide anion in cells. Ample of hepatotoxic drugs induces the liver damage by lipid peroxidation indirectly or directly. The proxy radicals are main factors that mediate lipid peroxidation leading to liver injury and kidney damage(41). MDA as a main reactive aldehyde appears during polyunsaturated fatty acid peroxidation in the biological

There are many ways for cancer to get in the body, like exposure to uranium and oxidative stress. [8]. When the mechanisms of the body loose the protein Glutathione it leads to making oxygen free radical neutral. Two of the most important proteins in the body are glutathione (GSH) and superoxide dismutase (SOD). Glutathione (GSH) works as an antioxidant [9]. Also, glutathione (GSH) has an important job that removes toxic metals out of the body because glutathione (GSH) has a sulphydryl group. This group strongly binds with toxic metals, effectively [3]. When uranium enters the body, it will reduce glutathione (GSH). When there is a reduction of glutathione (GSH), it leads to an increase of the

Under normal condition, ROS production in the brain is balanced by the endogenous enzymatic and non-enzymatic anti-oxidative mechanisms. The enzymes include superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase. SOD catalyzes dismutation of superoxide to hydrogen peroxide, providing the first line against ROS damage [46, 70]. GPX and catalase further metabolize hydrogen peroxide to water and oxygen [71]. In the process, reduced glutathione (GSH) is oxidized to oxidized glutathione (GSSG) and it can be recycled by the NADPH-dependent GSSG reductase [72]. Non-enzymatic endogenous anti-oxidative small molecules also play very important roles in defending against oxidative stress, especially in extracellular space that the enzymes are absent or in very low levels [73]. Small-molecule anti-oxidant can be water-soluble or lipid-soluble, these molecules include glutathione, vitamin E and C (inhibits

Based from observations made in the early 1950s, Denham Harman proposed that functional decline in cells and tissues was due to cumulative effects of macromolecular damage caused by oxygen radicals produced by respiratory enzymes (Harman 1956). This theory proposes that superoxide and other free radicals cause damage to the macromolecular components of the cell, resulting in accumulated damage to cause cells, and eventually organs, to stop functioning, leading to the aging phenotype (Sohal and Weindruch 1996, Clancy and Birdsall 2013). Oxidative damage is thought to occur from an imbalance when the antioxidant systems are unable to counter all the free radicals continuously generated during the life of the cell.

The kidney is greatly susceptible to damage caused by reactive oxygen species (ROSs), due to oxidative stress by polyunsaturated fatty acids in the composition of renal lipids (Ozbek, 2012). In addition this damage also can be caused by 1) high volume of blood flows through kidney and 2) large amounts of toxins

Risk factors such as smoking, hypercholesterolemia and hypertension have been proved to increase oxidative stress in the vessel (Davignon and Ganz, 2004). The oxidized LDL (ox-LDL) increases the synthesis of caveolin-1 and it inactivates endothelial NO synthase to produce NO. The free radical superoxide anion rapidly deactivates NO and destroys tetrahydrobiopterin, a cofactor for NO synthesis (Briasoulis et al., 2012). These result in inadequate blood flow into the arteries as the smooth muscle cells within the vessel walls can no longer relax sufficiently. Therefore, the total peripheral resistance in the arteries will increase (Hare and Stamler, 2005). Hypertension can be caused by high intake of salt. This raises both the osmolarity and body temperature, increases oxidative stress and causes damage to the vessel. Also, LDL and ox-LDL stimulate the production of reactive oxygen species (ROS) by inducing vascular endothelium inflammation and cause impaired endothelial function (Briasoulis et al., 2012). Smoking results in inflammation, thrombosis and oxidation of LDL, which increase oxidative stress in numerous cells. The reaction between NO and superoxide anion form peroxynitrire, the latter can cause vascular dysfunction(Mathur, 2010).Both active and passive exposure to smoking are reported to increase the risk of atherosclerosis and coronary heart disease by decreasing the

To be able to classify gout from other types of arthritis, it is a disease that is characterized by elevated levels of uric acid in the bloodstream. Elevated levels of uric acid, also known as MSU or monosodium urate, would cause them to crystallize and be deposited into the joints, tendons, and the tissues surrounding them, causing painful attacks that are recurring and, at times, can become so excruciatingly painful to the point of manifesting debilitation to those afflicted by it. The deposit of crystallized monosodium urate is referred to as tophus.

Along with the development of modern society and lifestyle activities, gout is formed by the impact of the environment and daily activities, is becoming many people's fears, so the understanding of the disease to early preventive measures, effective treatments play an extremely important role. Gout is a metabolic disease uric acid, leading to deposition of monosodium crystals in the organization (synovium and organizations around the joints, kidneys and kidney tissue tube), the contributory factors can find in some certain common medication, alcohol, and dietary foods (Gout 2016). The frequency of occurrence of gout increased significantly with age, and correlated with the increase of serum uric acid concentrations. The pathogenesis

Oxidative stress is widely accepted to be associated with dysfunction of pancreatic β-cells as well as insulin resistance in type 2 diabetes (Henriksen et al., 2011). Experimental evidences suggest the involvement of free radicals in the onset of diabetes and more importantly in the development of diabetic complications (Lipinsky, 2001). Studies have revealed decreases in expression of genes for antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase, and catalase in diabetic models (Lenzen et al., 1996). Also a decrease in the activities of the antioxidant/ antioxidant enzyme systems in diabetics are linked to the progressive glycation of the enzyme proteins (Hartnet et al., 2000). The interrelationship between the antioxidative potentials and antidiabetic activities of bioactive compounds is still unclear. In the present study, the extent of free radical damage orchestrated by STZ administration was significantly reduced by the antioxidant composition and combination treatment in a dose-dependent manner; thereby reducing the extent of pancreatic β-cell damages among the rats co-treated with combination therapy and STZ, relative to normal and STZ-only rats. The HFD/STZ-induced diabetic control rats had significantly lower (p< 0.05) of total SOD, CAT, GST and GPx activities among the extracts, cell gevity, antioxidant composition and combination therapy co-treated rats (Figure 4.2.34, Figure 4.2.35, Figure 4.2.36, Figure 4.2.37). HFD/STZ decreased the

2013). The exogenous purine pool is influenced significantly by ones diet, an increase in fructose consumption in both animals and humans have been shown to increase hepatic uric acid production (Cox et al.

antioxidant enzymes including small-molecule-weight antioxidants depends on cellular redox environment as it is a delicate process to regulate the two. ROS are responsible to regulate several physiological actions such as the ability to mediate and relate signal transduction from membrane receptors, At low concentrations, ROS are involved in regulating several physiological actions, including their ability to mediate relate signal transduction from membrane receptors, thus aiding the stimulation of several proteins and enzymes (1,2). Conversely, accumulation of extra intracellular ROS lead to oxidative stress, in turn will impair cellular membranes, promoting mitochondrial injury and cell death, which adversely impacting upon cell function and survival 3,5)

Hyperuricemia is a common human metabolic disorder in the production or excreation of uric acid , it leds to increase in serum uric acid levels more than the normal values (Haidari et al., 2012). Uric acid is the last metabolite of the purine catabolic pathway in humans. Uric acid is formed by oxidation of hypoxanthine to xanthine and xanthine to uric acid by the enzyme xanthine oxidase (XO). Hyperuricemia results in the deposition of urate crystals in the joint and kidney causing inflammation, gouty arthritis and uric acid nephrolithiasis (Tomita et al., 2000; Kong et al., 2002). The increasing risk of hyperuricemia also has been demonstrated in several studies that elevated serum uric acid levels predict the development of obesity and hypertension (Johnson et al., 2009; Perez-Pozo et al., 2010), hyperlipidaemia, cancer, and diabetes (Lin et al., 2000).

These dyslipidemias occur in about 25–60 % of gouty patients (32, 48). It is also worth remembering that two-thirds of the purines in the human are produced by cell and tissue turnover, whereas only one-third of purines are contributed by dietary intake. Excessive fructose intake has been implicated in the causation of the metabolic syndrome and gout (49, 50). Fructose-induced hyperuricemia has been known since the 1970s, but it has only recently been implicated in the causation of the metabolic syndrome and gout (51).

X.-M. Li, Department of Psychiatry, Faculty of Medicine, University of Manitoba, PZ432-771 Bannatyne Avenue, Winnipeg, Manitoba, Canada