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Biomedical subjects

J M Gutteridge

Publications and source records attributed to J M Gutteridge.

At least 163 records · Page 9Linked to original sources
PubMed1984

Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients.

Thiobarbituric acid (TBA)-reactive material is present in serum and knee joint synovial fluid from rheumatoid patients, consistent with lipid peroxidation occurring in vivo. The amount of TBA-reactive material in synovial fluid correlates with the concentration of iron salts present as determined by the bleomycin method, presumably because iron is an important catalyst of radical reactions in vivo. There appear to be significant correlations between the contents of TBA-reactive material and bleomycin-detectable iron in synovial fluid and the activity of rheumatoid arthritis as assessed with a clinical index of local inflammation and with various laboratory parameters.

Arthritis, Rheumatoid↗
PubMed1984

Non-protein-bound iron within bacterial cells and the action of bleomycin.

Damage to DNA by bleomycin in vitro is entirely dependent on the presence of an iron salt and molecular oxygen. This same reaction has been used to measure non-protein-bound iron in different bacterial species. Although several of the species examined were insensitive to the toxic effects of bleomycin, they all contained a concentration of non-protein-bound iron which should have been sufficient to allow iron-dependent damage to DNA. Other factors such as permeability or inactivation of the drug must explain their apparent insensitivity.

Bacillus subtilis↗
PubMed1983

Superoxide-dependent lipid peroxidation. Problems with the use of catalase as a specific probe for fenton-derived hydroxyl radicals.

Hydroxyl radicals (OH.) can initiate lipid oxidation by hydrogen abstraction. Transition metals however, particularly iron and copper, stimulate lipid oxidation by reacting with lipid peroxides to form new radical species. The haem-iron protein catalase can react non-specifically with lipid peroxides in this way resulting in loss of their conjugated diene structures. When a superoxide-generating system is used to stimulate lipid autoxidation, catalase can conceivably inhibit the reaction in two ways (A) by decomposing lipid peroxides as they are formed (B) through the removal of hydrogen peroxide preventing OH. radical formation. Results presented here suggest that the latter interpretation, although commonly presented, cannot be automatically assumed.

Catalase↗
PubMed1983

Copper salt-dependent hydroxyl radical formation. Damage to proteins acting as antioxidants.

Cupric ions (Cu2+) and ferric ions (Fe3+) added to hydrogen peroxide generate hydroxyl radicals (OH) capable of degrading deoxyribose with the formation of thiobarbituric acid-reactive products. This damage can be inhibited by catalase, OH radical scavengers and specific metal ion chelators. All proteins tested nonspecifically inhibited copper-dependent damage but have little effect on the iron-dependent reaction. Copper ions appear to bind to the proteins which prevents formation of OH radicals in free solution. However, OH radicals are still generated at a site-specific location on the protein molecule. Protein damage is detected as fluorescent changes in amino acid residues.

Albumins↗
PubMed1983

Effect of ferritin-containing fractions with different iron loading on lipid peroxidation.

Ferritin-containing fractions with different degrees of iron loading were prepared. All ferritin fractions stimulated the peroxidation of bovine brain phospholipid liposomes, as measured by the formation of thiobarbituric acid-reactive material. This stimulation was increased in the presence of ascorbate. Iron salts of equivalent concentration to those of the ferritin fractions were more stimulatory to lipid peroxidation at the higher iron concentrations. None of the fractions inhibited ascorbate-dependent peroxidation in the presence of added iron salts.

Ascorbic Acid↗
PubMed1983

Doxorubicin degradation: changes in activity compared by bacterial growth inhibition and free radical-dependent damage to deoxyribose.

Doxorubicin (DX) under partially anaerobic conditions can degrade deoxyribose with the release of thiobarbituric acid-reactive products. This activity is lost, together with the ability to inhibit bacterial growth, when DX is damaged by exposure to intense white light. Deoxyribose degradation may provide useful information about the anticancer properties of the drug.

Bacteria↗
PubMed1983

Ferroxidase and ascorbate oxidase activities of caeruloplasmin in synovial fluid from rheumatoid patients.

1. The protein caeruloplasmin inhibits certain free radical reactions, in part probably due to its ability to oxidize Fe2+ into Fe3+ (ferroxidase activity). Since caeruloplasmin is present in synovial fluid from rheumatoid patients, we investigated its properties in relation to protection of the joint from damage by oxygen radicals produced by activated phagocytes. 2. The ferroxidase and ascorbate oxidase activities of serum from both normal and rheumatoid patients could be accounted for by the caeruloplasmin present, as determined immunologically. More caeruloplasmin is present in the serum of rheumatoid patients than in normal serum. 3. Synovial fluid from rheumatoid patients contains caeruloplasmin protein but its ferroxidase and ascorbate oxidase activities are abnormally low. It is suggested that ferroxidase deficiency contributes to radical damage in the rheumatoid joint.

Arthritis, Rheumatoid↗
PubMed1983

Iron and oxygen radicals in tissue damage: implications for the neuronal ceroid lipofuscinoses.

The neuronal ceroid lipofuscinoses (NCL) are an important group of progressive encephalopathies characterized by accumulation of autofluorescent storage material, which probably arise during the destruction of cells by lipid peroxidation and the action of oxygen radicals such as superoxide (O.2-) and the hydroxyl radical (OH.). The rates of lipid peroxidation and of superoxide-dependent hydroxyl radical formation would be greatly accelerated by the presence of non-protein-bound iron salts. Cerebrospinal fluid from patients with different types of NCL has a higher level of non-protein-bound iron and lower antioxidant activity than that of controls. The raised iron content and decreased antioxidant protection found in cerebrospinal fluids may be symptomatic of a more general abnormality in iron metabolism and protection against its damaging effects.

Antioxidants↗
PubMed1983

Effect of a specific iron chelating agent on animal models of inflammation.

Iron is an important catalyst of oxidative radical reactions and promotes the formation of the hydroxyl radical from the superoxide anion radical and hydrogen peroxide. The stimulatory effect of the hydroxyl radical on lipid peroxidation prompted the speculation that free iron may directly promote inflammation and that iron chelating agents may have useful anti-inflammatory properties. This hypothesis is tested in animal models of inflammation with a specific iron chelating agent, desferrioxamine. At low doses (6 . 6 mg/kg) intraperitoneal desferrioxamine stimulated the induction of acute foot pad swelling in rats by monosodium urate but at higher doses (above 200 mg/kg) it suppressed this inflammatory reaction. A similar anti-inflammatory effect was observed in carrageenan-induced foot pad swelling. In guinea-pigs in which a Glynn-Dumonde synovitis was induced with bovine gammaglobulin, desferrioxamine (100 mg/kg) stimulated the acute inflammatory induction phase of this chronic allergic monoarthritis model. Repeated administration of desferrioxamine (100 mg/kg) from the seventh to the twelfth day after intra-articular challenge with bovine gammaglobulin markedly depressed the chronic inflammatory phase. In-vitro experiments suggest that desferrioxamine inhibits iron-catalysed lipid peroxidation when it is poorly saturated with iron, but loses this effect when it is iron saturated. Such an effect may explain our results with desferrioxamine in the animal studies and suggests that effective iron chelation and its removal may modify the inflammatory process in man.

Acute Disease↗
PubMed1982

The role of superoxide and hydroxyl radicals in phospholipid peroxidation catalysed by iron salts.

Iron(II) salts in aqueous solution, or iron(III) salts in the presence of an O.-2 generating system, can activate dioxygen to produce hydroxyl radicals. These are detected indirectly by their ability to degrade deoxyribose with the formation of thiobarbituric acid-reactive (TBA) products. Iron salts also catalyse the peroxidation of phospholipids resulting in the formation of TBA-reactive products. Hydroxyl radicals were responsible for the degradation of deoxyribose but not for the observed peroxidation of phospholipid. The function of O.-2 in both deoxyribose degradation and phospholipid peroxidation seems to be that of reducing iron(III) into iron(II).

Animals↗
PubMed1982

Superoxide-dependent formation of hydroxyl radicals and lipid peroxidation in the presence of iron salts. Detection of 'catalytic' iron and anti-oxidant activity in extracellular fluids.

Synovial fluid from rheumatoid patients and normal cerebrospinal fluid contains micromolar concentrations of non-protein-bound iron salts that can promote lipid peroxidation and also the superoxide-dependent formation of hydroxyl radicals from hydrogen peroxide. These iron catalysts of oxygen radical reactions cannot be detected by conventional assays unless interfering high-molecular-weight substances, probably proteins, are removed by ultrafiltration or inactivated by exposure to low pH values. The bleomycin assay for ;catalytic' iron [Gutteridge, Rowley & Halliwell (1981) Biochem. J.199, 263-265] does not suffer from these artifacts.

Animals↗
PubMed1982

The role of the superoxide and hydroxyl radicals in the degradation of DNA and deoxyribose induced by a copper-phenanthroline complex.

DNA degradation by a copper(II)-phenanthroline complex was studied in the presence of NADH, 2-mercaptoethanol or a mixture of hypoxanthine and xanthine oxidase, which generates the superoxide radical, O2-. In all cases degradation was prevented by catalase but not by scavengers of the hydroxyl radical, OH. It remains possible, however, that OH was generated in close association with DNA so that the scavengers could not remove it before it reacted. Superoxide dismutase inhibited DNA degradation at low copper (II) phenanthroline concentrations in the presence of NADH or hypoxanthine-xanthine oxidase, but not at higher complex concentrations. Superoxide dismutase had little effect on DNA degradation in the presence of 2-mercaptoethanol. The role of oxygen radicals in the DNA degradation induced by copper(II) phenanthroline is discussed.

Biotransformation↗