NMR studies on human, pathologically changed synovial fluids: Role of hypochlorous acid

Abstract

Recently, it has been reported that hypochlorous acid (HOCl), a special product of neutrophil myeloperoxidase, degrades N-acetyl groups of N-acetylglucosamine, chondroitin sulfate, hyaluronic acid, and minced articular cartilage via a transient product to acetate. This work concerns 1H NMR investigations of synovial fluids of patients with rheumatoid arthritis (RA). Synovial fluids of patients with severe forms of this disease are characterized by enhanced 1H NMR signals for N-acetyl groups (approximately 2.0 ppm) and acetate (1.90 ppm) and the appearance of a broad but less intense signal at 2.35 ppm. It is likely that this signal corresponds to the transient, chlorinated product of degradation of N-acetyl groups by hypochlorous acid. Moreover, 1H NMR signal intensities of N-acetyl groups and acetate strongly correlate with the myeloperoxidase activities in synovial fluids from patients with rheumatoid arthritis. These results have been confirmed by treatment of native sheep synovial fluid with sodium hypochlorite, resulting in the formation of the same resonances as observed in pathologically changed synovial fluids from humans. Thus, it is concluded that HOCl plays an important role for the cartilage degradation during rheumatoid arthritis.

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor

“…Oxidative stress induced by aberrant MPO activity has been observed in infl ammatory lung disease ( 8 ), rheumatoid arthritis ( 9,10 ), peripheral artery disease ( 11 ), cardiovascular disease ( 7,12 ), and diabetes ( 13,14 ). Even basic science studies in rats have shown that MPO directly correlates with severity of myocardial infarction ( 15,16 ).…”

In vivo MR spectroscopy using 3 Tesla to investigate the metabolic profiles of joint fluids in different types of knee diseases

“…A number of studies have used ex vivo nuclear magnetic resonance (NMR) spectroscopy on synovial fluid samples to investigate their metabolic profiles, 3 , 18 , 19 , 20 , 21 and a wide variety of low‐molecular‐mass components with ${\text{CH}}_2$ and ${\text{CH}}_3$ lipid peaks were identified in the samples 18 , 22 , 23 , 24 . In musculoskeletal lesions, the major metabolites are included in lipids with other metabolites.…”

Cartilage Degradation by Stimulated Human Neutrophils: Elastase Is Mainly Responsible for Cartilage Damage

“…Especially small degradation products like acetate or formate, which are formed when the polysaccharides of cartilage react with hypochlorite (11) or hydroxyl radicals (12), respectively, are difficult to detect. Here, sophisticated methods like high-resolution NMR spectroscopy are more appropriate analytical tools (16,17).…”