The onset of lipid peroxidation in rheumatoid arthritis: consequences and monitoring

Abstract

Several epidemiological studies propose the association of rheumatoid arthritis (RA) with oxidative stress. The aim of this study was to estimate the possible onset of systemic lipid peroxidation in RA patients and its relevance for pathophysiology and monitoring of RA. Seventy-three patients with RA and 73 healthy subjects were included in the study. Lipid peroxidation was estimated by the measurement of 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal, malondialdehyde, acrolein, crotonaldehyde, 4-oxononenal, and isoprostanes (8-isoPGF(2α)) levels. Cytosolic phospholipase A(2) (cPLA(2)), platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (GSH-Px) activities and vitamin E levels were also determined. In parallel, the plasma levels of phospholipid arachidonic acid (AA), linoleic acid (LA), and 4-HNE-protein adducts were monitored. Plasma of RA patients had increased vitamin E levels, but decreased GSH-Px activity and phospholipid AA and LA levels when compared to levels of the healthy subjects. The levels of aldehydes were significantly increased in the plasma of the RA patients and even more in urine. Significant increases in HNE-modified protein adducts was observed for the first time in plasma of RA patients, while the activities of PAF-AH and cPLA(2) were decreased. The 8-isoPGF(2α) levels were 9-fold higher in plasma and 3-fold higher in urine of RA patients and were related to the severity of disease. The levels of lipid peroxidation products in plasma and in urine suggest the relationship between lipid peroxidation and the development of RA. Additionally, urine 8-isoPGF(2α), plasma 4-HNE and 4-HNE-protein adducts appear to be convenient biomarkers to monitor progression of this autoimmune disease.

Reactive oxygen and nitrogen species in patients with rheumatoid arthritis as potential biomarkers for disease activity and the role of antioxidants

“…This may be attributed to the possible role of these reactive species in inflammatory reaction of RA [5]. These results may coincide with the results from previous studies that showed higher total oxidative stress in RA patients [36][37][38]. In our study, however, we have correlated the levels of each ROS with the biochemical markers of RA, with the hydroxyl radical having the strongest correlation, which is so far reported for the first time by this study.…”

“…In one study, the plasma levels of hydrogen peroxide was assessed as a marker of the total oxidative stress in RA patients who were unresponsive to DMARDs so that anti-tumor necrosis factor alpha (anti TNF-α) drugs were added to their treatment regimen [36]. In another study, the possible onset of lipid peroxidation and its relevance to the pathophysiology of RA was estimated [37]. Recently, the oxidative stress status in RA patients, supplemented with fish oil and primrose oil, compared with control RA patients was investigated through the assessment of the free radical formation and the levels of antioxidants in human serum [19].…”

Alpha-mangostin attenuates oxidative stress and inflammation in adjuvant-induced arthritic rats

“…During RA, the free radicals such as hydroxy radical, peroxynitrile, and hydrogen peroxide alter the lipid membrane structures and cause functional impairment of cellular components [14]. Lipid peroxidation is the key noxious event involved in RA [15].…”

Effect of Ozone in Freund’s Complete Adjuvant-Induced Arthritis

“…20,21 Several experimental studies have demonstrated that controlled O 3 administration could prevent the damage of reactive oxygen species. [5][6][7] Although the etiopathogenesis of RA has not been fully identified yet, oxidative stress plays an important role in its underlying pathogenesis. 11,[22][23][24] MDA, the oxidation product, is considered an index of lipid oxidation.…”

“…4 Recent evidence suggests that oxidative stress has an important role in the process of RA. [5][6][7] Therefore, in this study, we aimed to investigate the effectiveness and reliability of O 3 in Freund's complete adjuvant (FCA)-induced arthritis, an animal model for RA.…”