In vitro study of the antioxidant properties of non steroidal anti-inflammatory drugs by chemiluminescence and electron spin resonance (ESR).
OBJECTIVE
To determine the antioxidant activities of nonsteroidal anti-inflammatory drugs (NSAIDS), we examined by chemiluminescence (CL) and electron spin resonance (ESR) their scavenging properties towards lipid peroxides, hypochlorous acid and peroxynitrite.


METHODS
The antioxidant properties of nimesulide (NIM), 4-hydroxynimesulide (4-HONIM), aceclofenac (ACLO), 4-hydroxyaceclofenac (4-HOA-CLO), diclofenac (DICLO) and indomethacin (INDO) were tested on four different reactive oxygen species (ROS) generating systems: (I) phorbol-myristate acetate (PMA)-activated neutrophils, (II) Fe2+/ascorbate-induced lipid peroxidation, (III) HOCl-induced light emission, (IV) the kinetics of ONOO- decomposition followed by spectrophotometry. ROS production was monitored by luminol-enhanced CL or by ESR using two different spin traps.


RESULTS
At 10 microM, ACLO, NIM, 4-HONIM, 4-HOA-CLO, and DICLO decreased luminol-enhanced CL generated by PMA-activated neutrophils. Inversely, INDO increased the luminol enhanced CL. Interestingly, hydroxylated metabolites were more potent antioxidants than the parent drugs. Furthermore, all drugs tested, excepted ACLO, lowered lipid peroxidation induced by Fe2+/ascorbate system. ACLO and DICLO, even at the highest concentration tested (100 microM), did not significantly lower HOCl induced CL, whereas the other drugs were potent scavengers. Finally, all the NSAIDS accelerated decomposition of ONOO-, suggesting a potential capacity of the molecules to scavenge peroxynitrite.


CONCLUSIONS
The NSAIDs possess variable degrees of antioxidant activities, linked to their ability to react with HOCl, lipid peroxides or ONOO-. These antioxidant activities could offer interesting targeted side-effects in the treatment of joint inflammatory diseases.
Mouithys-Mickalad
A M
AM
Centre for Oxygen Research and Development (CORD), Institute of Chemistry, , University of Liège, Belgium.
Zheng
S X
SX
Deby-Dupont
G P
GP
Deby
C M
CM
Lamy
M M
MM
Reginster
J Y
JY
Henrotin
Y E
YE
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001205:Ascorbic Acid; D002713:Chlorine / Q000378:metabolism; D004008:Diclofenac / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007213:Indomethacin / Q000378:metabolism / Q000494:pharmacology; D007501:Iron; D007700:Kinetics; D015227:Lipid Peroxidation; D008163:Luminescent Measurements; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012973:Sodium Hypochlorite / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D005609:Free Radicals; D007202:Indicators and Reagents; D009566:Nitrates; D017382:Reactive Oxygen Species; D013449:Sulfonamides; C055891:4-nitro-2-(4'-hydroxyphenoxy)methanesulfonanilide; D004008:Diclofenac; C039642:peroxynitric acid; D002713:Chlorine; D012973:Sodium Hypochlorite; D007501:Iron; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid; C056498:aceclofenac; C012655:nimesulide; D007213:Indomethacin