Interaction and reactivity of urocanic acid towards peroxyl radicals (original) (raw)
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Free radical scavenging, DNA protection, and inhibition of lipid peroxidation mediated by uric acid
Annals of clinical and laboratory science, 2005
Uric acid (UA) has been proposed to be the dominant antioxidant in birds. The objective of this study was to investigate the quenching effect of varying concentrations of UA, including those found in avian plasma, on specific reactive oxygen species (ROS) and to determine the ability of UA to protect DNA and cellular membranes from ROS-mediated damage. Hydroxyl (OH) and superoxide (O2-) radicals were detected by electron spin resonance (ESR) and their presence was reduced following addition of UA (p <0.05) in a concentration-dependent manner. UA inhibited hydroxyl-mediated DNA damage, indicated by the presence of more precise, dense bands of lambda Hind III DNA after agarose gel electrophoresis and ethidium bromide staining (p <0.05). Lipid peroxidation of silica-exposed RAW 264.7 cell membranes was diminished (p <0.02) after addition of UA to the cell incubation mixture. These studies demonstrate that UA scavenges hydroxyl and superoxide radicals and protects against DNA d...
Chemico-Biological Interactions, 1990
Uric acid is an end-product of purine metabolism in Man, and has been suggested to act as an antioxidant in vivo. Products of attack upon uric acid by various oxidants were measured by high performance liquid chromatography. Hypochlorous acid rapidly oxidized uric acid, forming allantoin, oxonic/ oxaluric and parabanic acids, as well as several unidentified products. HOCI could oxidize all these products further. Hydrogen peroxide did not oxidize uric acid at detectable rates, although it rapidly oxidized oxonic acid and slowly oxidized allantoin and parabanic acids. Hydroxyl radicals generated by hypoxanthine/xanthine oxidase or Fe2+-EDTA/H202 systems also oxidized uric acid to allantoin, oxonic/oxaluric acid and traces of parabanic acid. Addition of ascorbic acid to the Fe2+-EDTA/H202 system did not increase formation of oxidation products from uric acid, possibly because ascorbic acid can 'repair' the radicals resulting from initial attack of hydroxyl radicals upon uric acid. Mixtures of methaemoglobin or metmyoglobin and H202 also oxidized uric acid: allantoin was the major product, but some parabanic and oxonic/oxaluric acids were also produced. Caeruloplasmin did not oxidize uric acid under physiological conditions, although simple copper (Cu 2÷) ions could, but this was prevented by albumin or histidine. The possibility of using oxidation products of uric acid, such as allantoin, as an index of oxidant generation in vivo in humans is discussed.
Urocanic acid as an efficient hydroxyl radical scavenger: a quantum theoretical study
Journal of Molecular Modeling, 2010
The photoisomerization of urocanic acid (UCA)which is present in human skin epidermis, where it acts as a sunscreen-from its trans isomer to its cis isomer upon exposure to UV-B radiation is known to cause immunosuppression. In recent years, the antioxidant properties of UCA (it acts as a hydroxyl radical scavenger) have also been recognized. In view of this, the mechanisms of stepwise reactions of trans-UCA with up to four hydroxyl radicals were investigated. The molecular geometries of the different species and complexes involved in the reactions (reactant, intermediate and product complexes, as well as transition states) were optimized via density functional theory in the gas phase. Solvation in aqueous media was treated with single point energy calculations using DFT and the polarizable continuum model. Single point energy calculations in the gas phase and aqueous media were also carried out using second-order Møller-Plesset perturbation theory (MP2). The AUG-cc-pVDZ basis set was employed in all calculations. Corrections for basis set superposition error (BSSE) were applied. Vibrational frequency analysis was performed for each optimized structure to ensure the validity of the optimized transition states. It was found that the binding of the first OH· radical to UCA involves a positive energy barrier, while subsequent reactions of OH· radicals are exergonic. Transition states were successfully located, even in those cases where the barrier energies were found to be negative. The cis-trans isomerization barrier energy of UCA and that of the first OH· radical addition to UCA are comparable, meaning that both processes can occur simultaneously. It was found that UCA could serve as an antioxidant in the form of an efficient OH· radical scavenger.
Archives of Biochemistry and Biophysics, 2000
Peroxynitrite, a biological oxidant formed from the reaction of nitric oxide with the superoxide radical, is associated with many pathologies, including neurodegenerative diseases, such as multiple sclerosis (MS). Gout (hyperuricemic) and MS are almost mutually exclusive, and uric acid has therapeutic effects in mice with experimental allergic encephalomyelitis, an animal disease that models MS. This evidence suggests that uric acid may scavenge peroxynitrite and/or peroxynitrite-derived reactive species. Therefore, we studied the kinetics of the reactions of peroxynitrite with uric acid from pH 6.9 to 8.0. The data indicate that peroxynitrous acid (HOONO) reacts with the uric acid monoanion with k ؍ 155 M ؊1 s ؊1 (T ؍ 37°C, pH 7.4) giving a pseudo-first-order rate constant in blood plasma k Urate /plasma ؍ 0.05 s ؊1 (T ؍ 37°C, pH 7.4; assuming [uric acid] plasma ؍ 0.3 mM). Among the biological molecules in human plasma whose rates of reaction with peroxynitrite have been reported, CO 2 is one of the fastest with a pseudo-first-order rate constant k CO2 /plasma ؍ 46 s ؊1 (T ؍ 37°C, pH 7.4; assuming [CO 2 ] plasma ؍ 1 mM). Thus peroxynitrite reacts with CO 2 in human blood plasma nearly 920 times faster than with uric acid. Therefore, uric acid does not directly scavenge peroxynitrite because uric acid can not compete for peroxynitrite with CO 2 . The therapeutic effects of uric acid may be related to the scavenging of the radicals CO 3 •؊ and NO 2 • that are formed from the reaction of peroxynitrite with CO 2 . We suggest that trapping secondary radicals that result from the fast reaction of peroxynitrite with CO 2 may represent a new and viable approach for ameliorating the adverse effects associated with peroxynitrite in many diseases.
Scavenging of Retinoid Cation Radicals by Urate, Trolox, and α-, β-, γ-, and δ-Tocopherols
International Journal of Molecular Sciences, 2019
Retinoids are present in human tissues exposed to light and under increased risk of oxidative stress, such as the retina and skin. Retinoid cation radicals can be formed as a result of the interaction between retinoids and other radicals or photoexcitation with light. It has been shown that such semi-oxidized retinoids can oxidize certain amino acids and proteins, and that α-tocopherol can scavenge the cation radicals of retinol and retinoic acid. The aim of this study was to determine (i) whether β-, γ-, and δ-tocopherols can also scavenge these radicals, and (ii) whether tocopherols can scavenge the cation radicals of another form of vitamin A—retinal. The retinoid cation radicals were generated by the pulse radiolysis of benzene or aqueous solution in the presence of a selected retinoid under oxidizing conditions, and the kinetics of retinoid cation radical decays were measured in the absence and presence of different tocopherols, Trolox or urate. The bimolecular rate constants a...
The Biochemical journal, 1996
Formation of peroxynitrite by the fast reaction between nitric oxide and superoxide anion may represent a critical control point in cells producing both species, leading to either down-regulation of the physiological effects of superoxide anion and nitric oxide by forming an inert product, nitrate, or to potentiation of their toxic effects by oxidation of nearby molecules by peroxynitrite. (The term peroxynitrite is used to refer to the sum of all possible forms of peroxynitrite anion and peroxynitrous acid unless otherwise specified.) In this report we demonstrate that, in spite of all the antioxidant defences present in human plasma, its interaction with peroxynitrite leads to generation of free radical intermediates such as (i) the ascorbyl radical, detected by direct EPR, (ii) the albumin-thiyl radical, detected by spin-trapping experiments with both N-tert-butyl-alpha-phenylnitrone and 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and (iii) a uric acid-derived free radical, detected...
5-Hydroxy-6-methyluracil, an Efficient Scavenger of Peroxyl Radical in Water
Current Organic Chemistry, 2009
The reactivity of 5-hydroxy-6-methyluracil (HMU) towards peroxyl radicals generated from the aerobic thermal decomposition of 2,2′-azo-bis(2-amidinopropane)dihydrochloride (AAPH) has been investigated. The oxidation product of HMU is dihydro-5,5,6-trihydroxy-6-methylpyrimidin-2,4-dion (94%). The relative oxidation rate of HMU vs. quercetin by peroxyl radicals generated from AAPH has been measured as 0.20 ± 0.04 at 54.6°C, hence HMU is the effective scavenger of peroxyl radicals. The overall kinetic parameters and the efficiency of radical generation from AAPH in water solution at pH 7.0 (0.1 M phosphate buffer) has been determined using HMU in temperature range 26°-84°C.
Antioxidants
Uric acid is considered the main substrate for peroxidases in plasma. The oxidation of uric acid by human peroxidases generates urate free radical and urate hydroperoxide, which might affect endothelial function and explain, at least in part, the harmful effects of uric acid on the vascular system. Peroxidasin (PXDN), the most recent heme-peroxidase described in humans, catalyzes the formation of hypobromous acid, which mediates collagen IV crosslinks in the extracellular matrix. This enzyme has gained increasing scientific interest since it is associated with cardiovascular disease, cancer, and renal fibrosis. The main objective here was to investigate whether uric acid would react with PXDN and compromise the function of the enzyme in human endothelial cells. Urate decreased Amplex Red oxidation and brominating activity in the extracellular matrix (ECM) from HEK293/PXDN overexpressing cells and in the secretome of HUVECs. Parallelly, urate was oxidized to 5-hydroxyisourate. It als...