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 A₂ (cPLA₂), 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 cPLA₂ 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.

KEYWORDS:

• 4-Hydroxy-2-nonenal
• 8-isoprostane
• plasma
• polyunsaturated fatty acid
• reactive aldehydes
• urine

Acknowledgements

This study was conducted with the use of equipment purchased by Medical University of Bialystok as part of the OP DEP 2007–2013, Project POPW 1.1-21, Contract No. POPW.01.01.00-20-002/09/01. The support from the side of the European Cooperation in Science and Technology project CM1001 is gratefully acknowledged. Genuine monoclonal mouse anti 4-HNE-His antibody in cell culture supernatant (clone 4-HNE 1g4; produced and kindly provided by the Institute of Molecular Biosciences, Austria).

Declaration of interest

The authors declare that they have no competing interest. This study was funded by a program grant from the Medical University of Bialystok.