Investigation of protein oxidation and lipid peroxidation in patients with rheumatoid arthritis

Abstract

We aimed to determine the importance of neutrophil activation and the source of oxidative stress in the pathogenesis of rheumatoid arthritis (RA) by quantification of advanced oxidation protein products (AOPP) and total thiol levels as markers of oxidative protein damage, malondialdehyde (MDA) levels as a marker of lipid peroxidation and myeloperoxidase (MPO) activity as a marker of neutrophil activation in patients with RA. Fifty-seven rheumatoid arthritis patients were included in the study and sub-grouped according to disease activity (active, n = 31; inactive, n = 26) and compared with healthy controls (n = 25). Serum MPO activity, AOPP, MDA, and thiol levels were measured by an enzymic spectrophotometric method. Serum MPO activity (p < 0.001), AOPP (p < 0.001), MDA (p < 0.001) and levels of thiol (p < 0.002), were higher in the patient group than the controls. Active and inactive RA groups were compared with the control group and there were significant differences between each parameter. MPO activity, AOPP, MDA and thiol levels were significantly higher in both active and inactive RA patients than the controls. On the other hand, when a comparison was made between active and the inactive stage, a statistically significant difference was present only in MDA (p < 0.05) and AOPP levels (p < 0.05). There was also a significant positive correlation between all parameters. These data strongly suggest that neutrophils, which constitute the most important source of chlorinated oxidants due to their high MPO content, may be involved in serum AOPP formation and therefore the production of a novel class of pro-inflammatory mediators of oxidative stress in RA patients and that protein oxidation could play an important role in the pathogenesis of RA as does lipid peroxidation.

Modern Pharmacological Approaches to Therapies: Substances Tested in Animal Models of Rheumatoid Arthritis

“…We used the substances reacting with thiobarbituric acid measured in plasma at 535nm (Brown & Kelly, 1996). Clinical studies have shown increased plasmatic levels of MDA in patients with RA (Baskol et al, 2005(Baskol et al, , 2006Sarban et al, 2005). The level of MDA in the plasma of arthritic animals was also elevated (Bauerova et al, 2008bHe et al, 2006;Sotnikova et al, 2009;Strosova et al, 2008Strosova et al, , 2009Tastekin et al, 2007).…”

Comparison of the usefulness of plasma levels of oxidatively modified forms of albumin in estimating kidney dysfunction in diabetic patients

“…1,7 IMA was first described as a marker of myocardial ischemia, but lately it is being intensively investigated in other disorders, including diabetes, and in other conditions associated with oxidative stress. 8,9 Increased AOPP and IMA formation are observed in different diseases and have been recognized as early markers and/or prognostic factors for numerous pathological conditions, such as acute coronary syndrome, systemic sclerosis, rheuamthoid arthritis, trauma, pulmonary embolism [10][11][12][13][14][15] .…”

Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease

“…Reactive oxidants are generated as a consequence of an "oxidative burst" of phagocytic cells (e.g., macrophages and neutrophils) activated by T. cruzi infection (8). NADPH oxidase, activated in all phagocytic cells, produces superoxide (O 2 ⅐ Ϫ ) (1,11). Endothelial activation of xanthine oxidase (XOD) in response to T. cruzi infection also results in increased O 2 ⅐ Ϫ production via oxidation of hypoxanthine to xanthine and uric acid (3,17).…”

“…⅐ NO, produced in abundance by iNOS, directly reacts with O 2 ⅐ Ϫ to form peroxynitrite (ONOO Ϫ ) and peroxynitrous acid (ONOOH), which have been shown to kill T. cruzi (36). Alternatively, nitrite (NO 2 Ϫ ), a major product derived from ⅐ NO, may be oxidized by MPO to nitrogen dioxide (NO 2 ⅐ ), which may further react with HOCl to form the highly reactive compound nitryl chloride (NO 2 Cl) (5).…”