Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. It affects the peripheral joints and is characterized by a chronic progressive inflammatory destruction of cartilage and subchondral bone, leading to erosive destruction of the joint cartilage and joint deformation. The experimental models of arthritis are widely used to investigate the pathogenesis of RA. The most common model of arthritis in rats is induced by immunization with native collagen II emulsified in Freund's adjuvant and called collagen induced arthritis (CIA). CIA is characterized by similar pathophysiological and pathobiochemical changes as RA in humans. The pathogenic mechanism of chronic inflammation is association with an increased production of autoantibodies, cytokines and activation of immune cells. In addition to cellular and humoral immunopatogical mechanisms of inflammation, metabolic processes play a significant role in the development of CIA. Although biochemical investigations are nonspecific, they are used for the determination of the stage of inflammation. In pathogenesis of tissue damage, an important role belongs to the oxidative and nitrosative stresses.

We examined the parameters of oxidative and nitrosative stresses in two groups of rats with CIA. One group (primary stage of CIA) consisted of 9 animals, second group (formed CIA) included 10 animals, the control group – 11 animals. The levels of hydrogen peroxide, the rate of generation of hydroxyl radical and the rate of generation of О2 •– were increased on primary stage of CIA in comparison with the control group. In primary stage of CIA the processes of lipid peroxidation were intensive, the level of MDA was higher compared to the control group. The activity of constitutive (calcium-dependent) de novo synthesis was lower compared with the control group. The intensity of inducible synthesis of nitric oxide was very high. Activity of calcium-dependent NO-synthase was higher in comparison with control group. Inducible NOS has the capacity to activate the processes of lipid peroxidation. The activation of lipid peroxidation by autoimmune diseases leads to formation of the significant amount of secondary autoantigens.

Besides, the level of physiologic constitutive synthesis of nitric oxide (oxidative metabolism of L-arginine due to percentage of сNOS) in blood serum of healthу animals was higher compared to rats with primary stage of CIA. The activity of arginase in this group was very high. We concluded, that nonoxidating arginase metabolism, that competes with oxidative NO-synthase metabolism of L-arginine, is activated. In group of rats with formed CIA the level of parameters of oxidative/nitrosative stresses was on the similar level as in group with primary stage of CIA. In animals with formed CIA only decrease of the synthesis of pathologic nitric oxide (determined due to the activity of inducible NO-synthase) and intensiveness of lipid peroxidation (determined due to MDA concentration) were noted compared to early stage of CIA. We recommend to use these parameters of oxidative and nitrosative stresses for the differential diagnosis of the stage of formation of chronic arthritis.

Ключові слова: rheumatoid arthritis, collagen-induced arthritis, active species of oxygen and nitrogen

Повний текст: PDF (Ukr)

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