ascorbic-acid and nimesulide

The antioxidant activities of different drugs like acetylsalicylic acid, nimesulide, dapsone, methlydopa, rifampicin and the well known antioxidants ascorbic acid and quercetin were assessed using the stable free radical alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH). DPPH is easily soluble at lower concentrations in methanol. It has a deep violet color. The changes in color are monitored calorimetrically. The measurements were made using HPLC at wavelengths 256 nm and 517 nm. The interactions between different drugs with DPPH were studied. All the compounds tested reduced DPPH. This method can be used to investigate oxygen free radical scavenging activity of drug candidates.

Topics: Antioxidants; Ascorbic Acid; Aspirin; Biphenyl Compounds; Chromatography, High Pressure Liquid; Dapsone; Free Radicals; Methyldopa; Picrates; Quercetin; Rifampin; Spectrophotometry, Ultraviolet; Sulfonamides

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.. 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.. 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.. 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.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ascorbic Acid; Chlorine; Diclofenac; Electron Spin Resonance Spectroscopy; Free Radicals; Humans; In Vitro Techniques; Indicators and Reagents; Indomethacin; Iron; Kinetics; Lipid Peroxidation; Luminescent Measurements; Neutrophil Activation; Neutrophils; Nitrates; Reactive Oxygen Species; Sodium Hypochlorite; Spectrophotometry, Ultraviolet; Sulfonamides; Tetradecanoylphorbol Acetate

The superoxide and hydroxyl radical scavenging activities of nimesulide (CAS 51803-78-2) and its main metabolite 4-hydroxynimesulide (CAS 109032-22-6) were investigated by Electron Spin Resonance (ESR) spectroscopy, with the spin trapping technique. Hydroxynimesulide is a good scavenger of both O2 degrees- (IC50 = 40 mumol/l) and HO degree (IC50 = 54.8 mumol/l) radicals, and its high reactivity towards HO degree was confirmed by the rate constant for reaction with HO degree (K = 8.9 x 10(10) mol-1 l s-1) determined by competition kinetic studies with 5,5-dimethyl-l-pyrroline-N-oxide. Nimesulide, which has been shown by ESR to be inactive as a superoxide quencher, has a rate constant of reaction with HO degree slightly greater than that of its metabolite (3.3 x 10(11) mol-1 l s-1). In the HO degree-induced peroxidation of phosphatidylcholine (PC) liposomes, both compounds act as potent preventive antioxidants, but the HO degree entrapping capacity of the parent drug was again greater than that of hydroxynimesulide (IC50 2.12 vs 3.84 mumol/l). The metabolite is also a potent scavenger of the peroxyl radical (ROO degree) in the propagation phase of PC peroxidation (marker conjugated dienes), with an IC50 = 2.67 mumol/l; at 5 mumol/l it induces a lag time in the decomposition of PC hydroperoxides (PC-OOH) into aldehydic products of 40 h longer than in the controls (markers: conjugated dienes and total carbonyl functions). In PC liposomes, in the presence of preformed PC-OOH, the metabolite prevents PC peroxidation stimulated by 5 mumol/l Fe2+, via the Fenton reaction (marker: conjugated dienes), at the micromolar level (IC50 = 17 mumol/l) through an anti-free radical activity and a free iron chelating mechanism. Hydroxynimesulide in fact interacts with Fe2+ ions, giving rise to a strong complex, with a stability constant (log K) estimated to be around 8/9. In addition, hydroxynimesulide efficiently protects ex vivo synovial fluid lipids from the oxidative stress induced by Fe2+/ascorbate, already at 10 mumol/l (marker: thiobarbituric acid reactive substances). These results provide evidence for strong antioxidant and iron-chelating properties of 4-hydroxynimesulide, which can act synergistically with the specific HO degree scavenging activity of the parent drug in preventing and limiting in vivo the free radical-mediated tissue damage in both acute and chronic inflammatory situations.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ascorbic Acid; Depression, Chemical; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Humans; Hydroxyl Radical; In Vitro Techniques; Iron; Kinetics; Lipid Peroxidation; Peroxides; Phosphatidylcholines; Reactive Oxygen Species; Sulfonamides; Superoxides; Synovial Fluid

In 39 outpatients suffering from a seasonal epidemic influenza, the antipyretic, analgesic and anti-inflammatory activity of nimesulide granules was compared with that of aspirin + vitamin C granules. The drugs were administered b.i.d., dispensed in one-dose sachets containing either 100 mg of nimesulide or 500 mg aspirin + 300 mg vitamin C. The efficacy of the two treatments was comparable: both drugs brought about a rapid complete recovery in all treated patients. However, nimesulide was better tolerated: only one case of slight gastralgia was recorded in the nimesulide group vs the six cases of side-effects complained of in the aspirin + vitamin C group.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Ascorbic Acid; Aspirin; Body Temperature; Female; Humans; Influenza, Human; Male; Middle Aged; Sulfonamides