Scavenging of Free Radicals by Tenoxicam: A Participating Mechanism in the Antirheumatic/Antiinflammatory Efficacy of the Drug

Abstract

The radical scavenging activity of tenoxicam against hydroxyl (HO.), superoxide (O2.-), and peroxyl (LOO.) radicals, all of them involved in the inflammatory reactions, has been tested in different cell-free systems and by different techniques. Tenoxicam is a good scavenger of both HO. radicals (IC50 = 56.7 microM), as determined by Electron Spin Resonance (ESR) spectroscopy with the spin trapping (5,5-dimethyl-1-pyrroline N-oxide, DMPO) technique, and O2.- radicals generated by the phenazine methosulfate/reduced beta-nicotinamide adenine dinucleotide (PMS/NADH) system. The high reactivity of the drug towards HO. was confirmed by the rate constant of reaction with HO. (k approximately 10(10) M-1s-1), determined by competition kinetic studies with N,N-dimethyl-4-nitrosoaniline. In addition at a microM level (1-5 microM) it dose-dependently prevents the phycoerythrin peroxidation induced by the water-soluble azoinitiator 2,2-azobis (2-amidinopropane) dihydrochloride (ABAP), indicating a quenching effect on aqueous peroxyl radicals. The HO.-entrapping capacity was confirmed in models more close to the in vivo situation: tenoxicam inhibits the HO.-induced depolymerization of hyaluronic acid already at 15 microM and the HO.-driven lipid peroxidation in phosphatidylcholine liposomes (PCL) with an IC50 of 10 microM. In this membrane model it delays at 1-10 microM level the decomposition of phosphatidylcholine hydroperoxides to short-chain alkenals (markers: total carbonyl functions as 2,4-dinitrophenylhydrazones and conjugated dienes). The high susceptibility of the drug to HO. attack is also demonstrated by its extensive degradation (HPLC studies) when irradiated with HO. radicals. The antioxidant component of tenoxicam evidenced in this study sheds some light on the hitherto undefined mechanism of the antiinflammatory action of the drug.

Characterization of phenolic antioxidants from Maté ( Ilex Paraguayensis ) by liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry

“…The antioxidant activity of the extract was evaluated first by monitoring its ability in quenching the stable free radical DPPH, according to the method previously described, 7 i.e. loss of absorbance at 517 nm of an ethanol solution of DPPH, in the presence and the absence of increasing concentrations of Maté extract or other scavengers (chlorogenic acid, ascorbic acid, vitamin E).…”

Evaluation of immunomodulatory activity of tenoxicam in mice

“…The maximum inflammatory response was observed in DTH against DNCB Tenoxicam has demonstrated inhibition of the production of prostaglandins from inflammatory tissues [14,15]. Less production of inflammatory mediators could be the reason of decreased response to DNCB.…”

Synthesis and Biologic Evaluation of Substituted 5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one Derivatives as Selective COX‐2 Inhibitors: Molecular Docking Study

“…The different concentrations (10,15,20,25 lg/mL) of tested compound were taken in volume of 200 lL. Nitric oxide production was initiated with the addition of 200 lL of phosphate buffer (0.1 M, pH 7.4) and 800 lL sodium nitroprusside (10 ml), and the reaction mixture was incubated at 25°C for 150 min.…”

“…It has been reported that in inflammatory disorders, excessive free radical generation takes place and several NSA-IDs and pyrazolone compounds with anti-inflammatory activity are reported to act as radical scavengers (25). Therefore, antioxidant property of the synthesized pyrazolones was evaluated using DPPH, nitric oxide, and hydrogen peroxide radical-scavenging in vitro assays (26,27).…”