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OXIDATIVE STRESS

Oxidative stress is well known to be involved in the pathogenesis of lifestyle-related diseases, including aging, atherosclerosis, hypertension, diabetes mellitus, ischemic diseases, neurodegeneration and/or malignancies.

In normal physiological situations, Radical Oxygen Species (ROS) are constantly produced in our organism, where they even play several physiological roles, and their production is regulated by an efficient antioxidant defense (vitamins, trace elements, proteins and enzymes) to prevent excessive cell damage. 

Toxic effects of free radicals can affect either changes in intracellular redox potential, gene activation and oxidative modification of lipids, proteins and DNA. Most of the pro-oxidative markers belong to the latter mechanism. Lipids are reported as one of the primary targets of ROS. 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 magnesium to form stable aldehydes, such as malondialdehyde (MDA), that damage cell membranes or lipoproteins (oxidized LDLs). 
Oxidative damages of DNA that are most frequently manifested by base loss and formation of abasic sites (AP site), unilateral cleavage of DNA chain and sugar modification. These modifications can also lead to DNA double strand bilateral breakage that is a highly mutagenic event. The most commonly used marker of oxidatively modified DNA molecule is 8-hydroxy-2’-deoxyguanosine (8-OHdG).

As a marker of production, activity of several enzymes aimed at generating free radicals can also be measured (xanthine oxidase (XDH), myeloperoxidase (MPO), NADPH oxidase (NOX)).

Anti-oxidants constitute the major defense system of our organism against ROS and free radicals. 

To evaluate anti-oxidant defenses level, different subset of markers must be evaluated :
– Enzymes strongly involved in free radicals and peroxide detoxification such as superoxide dismutase (SOD1, SOD2), glutathione peroxidase (GPX), catalase, thioredoxin reductase (TRXND) and glutathione pathway enzymes (glucose-6-phosphate dehydrogenase (G6PD), glutathione synthase (GSS) and glutathione reductase (GSR))

– small molecules able to scavenge free radicals such as carotenoids (vitamin A and β-carotene), vitamin C, vitamin E (α and γ), glutathione (GSH) and its oxidised product (GSSG), uric acid, bilirubin, coenzyme Q10, trace elements such as selenium that plays an important role as part of anti-oxidant selenoproteins.

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