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Biomedical subjects

R L Willson

Publications and source records attributed to R L Willson.

At least 37 records · Page 2Linked to original sources
PubMed1986

Thiyl free radicals and the oxidation of ferrocytochrome c. Direct observation of coupled hydrogen-atom- and electron-transfer reactions.

Absolute rate constants for the reaction of ferrocytochrome c with the thiyl radicals derived from cysteine, GSH, penicillamine and N-(2-mercaptopropionyl)glycine were measured by using the technique of pulse radiolysis. The reaction is believed to occur through a one-electron-transfer process, in agreement with the hypothesis that thiols may act as catalysts linking hydrogen-atom- and electron-transfer reactions.

Cytochrome c Group↗
PubMed1985

Organic free radicals and proteins in biochemical injury: electron- or hydrogen-transfer reactions?

The reactions of organic free radicals, acting as either reductants or oxidants, have been studied by pulse radiolysis in neutral aqueous solution at room temperature. Manyhydroxyl-substituted aliphatic carbon-centred radicals and one-electron adducts have been shown to be good one-electron reductants, while several oxygen-, sulphur- and nitrogen- (but not carbon-) centred free radicals have been shown to be good one-electron oxidants. Several carbon-centred radicals can be reduced rapidly by hydrogen transfer, from undissociated thiol compounds which can thus act as catalysts facilitating the overall reduction of a carbon-centred radical by an electron-donating molecule. Kinetic considerations influenced by the one-electron redox potentials of the radical-molecule couples involved, determine whether a particular reaction predominates. In this paper examples of such reactions, involving a water-soluble derivative of vitamin E (Trolox C) and the coenzyme NADH, are described, together with studies showing (a) that even in complex multi-solute systems some organic peroxy radicals can inactiviate alcohol dehydrogenase under conditions where the superoxide radical does not, and (b) the superoxide radical can be damaging if urate is also present, and this damage can be reduced by the presence of superoxide dismutase.

Alcohol Dehydrogenase↗
PubMed1985

Peroxy free radicals, enzymes and radiation damage: sensitisation by oxygen and protection by superoxide dismutase and antioxidants.

In vitro studies have shown that in the presence of the DNA base thymine, the enzyme alcohol dehydrogenase can be extensively damaged by exposure to only 1 gray of cobalt-60 gamma radiation. When irradiated solutions are purged with oxygen-free nitrogen or contain the enzyme superoxide dismutase or various antioxidants, the extent of inactivation of the dehydrogenase is considerably reduced. Peroxy free radicals are considered to be responsible for the inactivation and cysteine and methionine residues are considered the most likely sites of initial damage. The results presented, with those obtained with ADP and urate instead of thymine and with various amino acids and foreign compounds, are discussed in the light of previous statements concerning the relevance of enzyme damage in radiobiology and the role of oxygen free radicals in tissue injury generally.

Alcohol Dehydrogenase↗
PubMed1984

Uric acid substantially enhances the free radical-induced inactivation of alcohol dehydrogenase.

Lactate dehydrogenase (LDH) and yeast alcohol dehydrogenase ( YADH ) are inactivated when attacked by hydroxy free radicals (OH). Organic molecules with a high rate constant of reaction with OH such as ascorbate or urate can compete with the enzymes for these strongly oxidising radicals. However, although 10(-3)M ascorbate can substantially protect both LDH and YADH from OH attack, in the presence of 10(-3)M urate only LDH is protected. In the case of YADH an even greater degree of inactivation than with OH occurs. The extent of inactivation is considerably reduced when oxygen is absent, in agreement with a urate peroxy radical perhaps being partly responsible for the increased inactivation of the enzyme.

Alcohol Dehydrogenase↗
PubMed1983

Reaction of the trichloromethyl and halothane-derived peroxy radicals with unsaturated fatty acids: a pulse radiolysis study.

The absolute rates of reaction of the trichloromethylperoxy radical, CCl3OO., derived from carbon tetrachloride and the halothane peroxy radical, CF3CHClOO., with oleic, linoleic, linolenic and arachidonic acids have been determined using the fast reaction technique of pulse radiolysis. In general, the rates of reaction of the radical derived from carbon tetrachloride are approximately five times greater than those for the halothane related radical. In both cases the rate constant increases with increasing unsaturation of the fatty acid in agreement with the known greater susceptibility of polyunsaturated fatty acids to peroxidative decomposition.

Carbon Tetrachloride↗
PubMed1983

Stimulation of microsomal lipid peroxidation by iron and cysteine. Characterization and the role of free radicals.

The stimulation of microsomal lipid peroxidation by FeSO4 and cysteine has been investigated. Although both FeSO4 and cysteine alone promoted an increase in malonaldehyde production, when these agents were added together to microsomes the resultant level of malonaldehyde was greater than the sum of the amounts formed by these pro-oxidants when acting individually. A further indication of an interaction between FeSO4 and cysteine was shown by the inhibitory action of chelating agents. Stimulation of peroxidation was shown to be independent of microsomal protein, including cytochrome P-450. The system has been characterized for the effects of cysteine, Fe2+ and O2 concentrations, pH, temperature and antioxidants. The results indicate that the high level of peroxidation attained with this system, its non-enzymic character and the involvement of hydroxyl radicals make it particularly useful for the investigation of the action of antioxidants. Furthermore it may also be a model of way in which decompartmentalized, delocalized or 'free' iron initiates peroxidation in vivo.

Animals↗
PubMed1983

Antiinflammatory drugs: protection of a bacterial virus as an in vitro biological measure of free radical activity.

The effects of the hydroxyl free radical (OH), the superoxide free radical (O2-) and the trichloromethyl peroxy free radical (CC13O2) on the survival of bacteriophage T2 have been studied in the absence and presence of several non-steroidal anti-inflammatory drugs (NSAID). The trichloromethylperoxy radical derived from carbon tetrachloride is considerably more effective than the hydroxyl radical in inactivating the virus: the superoxide radical has only a minor inactivating effect. All the NSAID investigated (flurbiprofen, ibuprofen, sulindac, piroxicam, benoxaprofen, mefenamic acid, diflunisal, aspirin, D-penicillamine, indomethacin and metiazinic acid) inhibit inactivation by OH. This is in agreement with the high rate constants of reaction with this radical determined using the fast reaction technique of pulse radiolysis, i.e. (k greater than 10(9) M-1 S-1). The sulphur-containing drugs, metiazinic acid, piroxicam, penicillamine and sulindac as well as the indole derivative indomethacin, protect the virus from inactivation by the model peroxy radical CC13O2 (the dose modifying factor, DMF greater than 20). In contrast, acetylsalicylic acid related drugs, such as diflunisal, the anthranilic acid derivative, mefenamic acid, and some phenylpropionic acid derivatives, such as flurbiprofen, exhibit only a very small or no protective effect (DMF less than 2). As with OH, the ability of the drugs to protect the virus from inactivation by the peroxy radical is in agreement with their corresponding rate constants of reaction determined by pulse radiolysis.

Anti-Inflammatory Agents↗
PubMed1983

Free radical protection: why vitamin E, not vitamin C, beta-carotene or glutathione?

There is increasing evidence that as a result of infection or the action of toxic chemicals or radiation, the body may be continuously exposed to the damaging action of free radicals. While previous results have suggested that zinc may be involved in limiting the formation of these highly reactive species, natural organic antioxidants such as vitamin E may also play an important role in reducing their effect. Recent results showing quantitative and qualitative differences in the free radical reactivity of vitamin E, vitamin C, beta-carotene and glutathione are reported. The possibility that in vivo these compounds may sometimes act synergistically is discussed in the light of recent information on hydrogen atom and electron transfer reactions and the long-established findings that vitamin C can augment the antioxidant action of vitamin E whereas iron salts can have a deleterious effect.

Animals↗
PubMed1981

Cytotoxicity of metronidazole (Flagyl) and misonidazole (Ro-07-0582): enhancement by lactate.

The cytotoxic activity of metronidazole (Flagyl) and misonidazole (MISO) to hypoxic Chinese hamster ovary (CHO) cells suspended in standard medium in sealed vials and in gassed spinner flasks has been investigated. Flagyl (5 mM) was only cytotoxic at high initial cell densities. However, when lactate (20 mM) was included in the medium the cytotoxicity of Flagyl at low cell densities was considerable, and similar to that of misonidazole under the same conditions. The relevance of this "lactate effect" to in vivo systems, and the possible mechanisms involved, are discussed.

Animals↗
PubMed1981

Reactions of the trichloromethylperoxy free radical (Cl3COO) with tryptophan, tryptophanyl-tyrosine and lysozyme.

The trichloromethyl peroxy radical Cl3COO reacts with tryptophan, tryptophanyl-tyrosine and with lysozyme to form products whose overall absorption spectrum is different from those observed following the reaction of hydroxyl, bromide, thiocyanate or azide radicals. Two spectral components have been identified: a minor component attributed to the neutral tryptophanyl radical which can react with ascorbate and intramolecularly with tyrosine residues and a major component which does not undergo either of these reactions and is probably a radical adduct.

Dipeptides↗