The role of N-acetylcysteine in protecting synovial fluid biomolecules against radiolytically-mediated oxidative damage: a high field proton NMR study.
High field proton (1H) NMR spectroscopy has been employed to evaluate the abilities of the antioxidant thiol drug N-acetylcysteine and exogenous cysteine to protect metabolites present in intact inflammatory synovial fluid samples against oxidative damage arising from gamma-radiolysis (5.00 kGy) in the presence of atmospheric O2. Although oxidation of urate to allantoin by radiolytically-generated *OH radical was readily circumventable by pre-treatment of synovial fluids with N-acetylcysteine (1.00 or 3.00 x 10(-3) mol x dm(-3)) or cysteine (1.00, 2.00 or 5.00 x 10(-3) mol x dm(-3)), both thiols offered only a limited protective capacity with respect to hyaluronate depolymerisation and the production of formate from carbohydrates in general. Radiolytic products generated from the added thiols (predominantly their corresponding disulphides) were simultaneously detectable in 1H Hahn spin-echo spectra of gamma-irradiated synovial fluids, permitting a quantitative evaluation of the radioprotective capacity of these agents. It is concluded that the multicomponent analytical ability of high field 1H NMR spectroscopy provides much useful molecular information regarding mechanisms associated with the radioprotectant actions of thiols in intact biofluids.
Grootveld
M
M
Inflammation Research Group, St. Bartholomew's and the Royal London Hospitals School of Medicine and Dentistry, UK. c.j.silwood@mds.qmw.ac.uk
Silwood
C J
CJ
Lynch
E J
EJ
Patel
I Y
IY
Blake
D R
DR
D000111:Acetylcysteine / Q000378:metabolism* / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D005609:Free Radicals; D005720:Gamma Rays; D006801:Humans; D007719:Knee Joint; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D018384:Oxidative Stress; D011522:Protons; D013438:Sulfhydryl Compounds; D013582:Synovial Fluid / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects
D005609:Free Radicals; D011522:Protons; D013438:Sulfhydryl Compounds; D003545:Cysteine; D000111:Acetylcysteine