**1.2 Role of antioxidant systems and endogenous antioxidants in remission of rheumatoid arthritis**

Epidemiological studies have shown that RA occurs in previously healthy subjects who had low levels of circulating antioxidants [11], implying a pathogenic role of increased OS in the development of RA. Patients with RA have been reported to have lower serum levels of a variety of antioxidants, including vitamin E, vitamin C, β-carotene, selenium, and zinc, in comparison with healthy individuals [12]. In order to prevent the damaging effect of prooxidants, the body has an antioxidant defense system that protects cellular systems from oxidative damage [13]. Some common enzymes that are involved in the neutralization of free radicals are endogenous enzymatic antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), and peroxiredoxins. These enzymes neutralize hydrogen peroxide, yielding water (CAT, GPx) and oxygen (CAT) molecules. The nonenzymatic endogenous antioxidants taking part in the first line of defense belong to preventive antioxidants, and in blood plasma they are represented by metal-binding proteins as ceruloplasmin, ferritin, lactoferrin, transferrin, and albumin. These proteins inhibit the formation of ROS by binding with transition metal ions (e.g., iron and copper). Also, metallothionein plays an essential role in the prevention against ROS. The second line of defense against ROS involves nonenzymatic antioxidants that are represented by molecules characterized by the ability to rapidly inactivate radicals and oxidants. The third line of defense consists of repair mechanisms against damage caused by free radicals. This form of protection is provided by enzymatic antioxidants, which can repair damaged DNA and proteins, fight against oxidized lipids, stop chain propagation of peroxyl lipid radicals, and repair damaged cell membranes and molecules [14]. Dietary antioxidants (vitamins C and E, carotenoids, polyphenols, and biogenic elements) can affect the activity of endogenous antioxidants. Endo- and exogenous antioxidants may act synergistically to maintain or re-establish redox homeostasis. The major endogenous nonenzymatic low-molecular-mass antioxidants include glutathione, uric acid, melatonin, coenzyme Q, bilirubin, and polyamines. Considering the mechanism of antioxidant protection, the endogenous substances

can be divided into true scavengers, metal-buffering proteins, and chelators of redox-stable metals [13]. This chapter is focused on evaluating coenzyme Q10 and hyaluronan of different molecular weight in experimental arthritis induced in rats.
