**2. Pathophysiology of free radicals**

When there is an imbalance between free radical production and removal, causing oxidative and resulting in aberrant metabolic processes in the body. To neutralize and eradicate the free radicals, enzymatic and non-enzymatic antioxidants such as vitamin E (tocopherols and tocotrienols), SOD, CAT, GPx, vitamin C (ascorbic acid), betacarotene (β-carotene), coenzyme Q10 (CoQ10), play an important role in the body's defense system against these toxic species. Thus, these biological molecules demonstrate an essential role in the quenching or removal of harmful free radicals. Antioxidants such as polyphenolic compounds can reduce the concentration of ROS by scavenging them, and hence potentially averting any deleterious oxidative damage to macromolecules [2]. Several degenerative conditions such as cardiovascular, neurological, diabetes, ischemia-reperfusion injury and aging have been shown to be caused by pathophysiology of free radicals. Autoimmune diseases (ADs) such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are prominent examples where free radicalinduced damage occurs in cells and tissues [10]. The diseases, which are caused by free radical, are usually characterized into two categories: one relating to cancer and diabetes involving "mitochondrial oxidative stress" and occur due to impaired glucose tolerance while the second category involves inflammatory oxidative conditions resulting in atherosclerosis and chronic inflammation. Mutation in DNA, which more often occurs due to oxidative damage is strongly correlated to the etiology of cancer, and is one of the initiators of carcinogenesis in which elevated levels of DNA lesions become apparent in many tumors. ROS-induced changes are also found in various diseases of the heart such as cardiomyopathy, ischemic heart disease, hypertension, atherosclerosis, and heart failure [1]. Several studies have established the key role of oxidative stress in the pathology of the joints which includes inflammatory infiltration, synovial proliferation, and angiogenesis [11, 12].
