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J M Gutteridge

Publications and source records attributed to J M Gutteridge.

At least 73 records · Page 4Linked to original sources
PubMed1993

Antioxidant protection against organic and inorganic oxygen radicals by normal human plasma: the important primary role for iron-binding and iron-oxidising proteins.

Normal human plasma contains numerous high and low molecular mass redox active molecules that are able to react rapidly with organic and inorganic oxygen radicals. The ability of such plasma molecules to substantially inhibit, or delay, free radical mediated oxidation of added substrates has led to their classification as important biological antioxidants. Using phospholipids to detect organic oxygen radicals, and deoxyribose to detect inorganic oxygen radicals, we here show that the primary antioxidants of normal human plasma reside mainly in two plasma proteins representing no more than 4% of the total proteins present. The iron-binding properties of transferrin and the iron-oxidising properties of caeruloplasmin, at a reaction dilution of 1:50, offer considerable protection against organic and inorganic oxygen radicals generated by iron and ascorbate. Plasma thiol group-containing molecules, at concentrations well below those that would be required to compete with the detector molecule (based on known second order rate constants for reaction with hydroxyl radicals) inhibited damage to deoxyribose, but stimulated damage to phospholipids.

Antioxidants↗
PubMed1993

Lipoprotein oxidation: the 'fruit and vegetable gradient' and heart disease.

Coronary heart disease is a major cause of premature death in Western societies. Oxidation of low density lipoproteins by oxygen free radicals provides a molecular link to the development of atherosclerosis. Free radical oxidations can usually be protected against by appropriate antioxidants. Recent studies suggest epidemiological correlations exist between the levels of plasma antioxidant vitamins and mortality from heart disease.

Free Radicals↗
PubMed1992

Antioxidant protection against organic and inorganic oxygen radicals by normal human plasma: the important primary role for iron-binding and iron-oxidising proteins.

Normal human plasma contains numerous high- and low-molecular-mass redox-active molecules that are able to react rapidly with organic and inorganic oxygen radicals. The ability of such plasma molecules to substantially inhibit, or delay, free-radical mediated oxidation of added substrates has led to their classification as important biological antioxidants. Using phospholipids to detect organic oxygen radicals and deoxyribose to detect inorganic oxygen radicals, we here show that the primary antioxidants of normal human plasma reside mainly in two plasma proteins representing no more than 4% of the total proteins present. The iron-binding properties of transferrin and the iron-oxidising properties of caeruloplasmin, at a reaction dilution of 1:50, offer considerable protection against organic and inorganic oxygen radicals generated by iron and ascorbate. Plasma thiol-group-containing molecules, at concentrations well below those that would be required to compete with the detector molecule (based on known second-order rate constants for reaction with hydroxyl radicals) inhibited damage to deoxyribose, but stimulated damage to phospholipids.

Antioxidants↗
PubMed1992

Biologically relevant metal ion-dependent hydroxyl radical generation. An update.

Transition metal ions, especially iron, appear to be important mediators of oxidative damage in vivo. Iron(II) reacts with H2O2 to give more-reactive radicals. On the basis of ESR spin-trapping data with DMPO, supported by aromatic hydroxylation studies and patterns of DNA base modification, it is concluded that hydroxyl radical (OH.) is likely to be the major damaging species formed in Fenton Systems under biologically-relevant conditions (which include iron concentrations no higher than the micromolar range). Although reactive oxo-iron species (such as ferryl and perferryl) may also be important, direct chemical evidence for their formation and identity in biologically relevant Fenton systems is currently lacking. Studies at alkaline pH values show that iron(IV) and iron(V) species are highly oxidizing under those reaction conditions, with a pattern of reactivity different from that of OH..

Free Radicals↗
PubMed1992

Iron and oxygen radicals in brain.

The brain has been shown to contain regions with high concentrations of non-heme iron, and some of this iron can be chelated, which suggests that it is in a low molecular mass form. The chelatable iron appears to be responsible for the in vitro peroxidation of homogenized brain tissue lipids. It has been suggested that low molecular mass iron is essential for normal brain functions, and that iron is present in the reduced ferrous state. Recent studies have shown that chelatable iron is often present in micromolar concentrations in apparently normal cerebrospinal fluids (CSF), and that this iron is often increased in certain neurological diseases. Using a molecular recognition assay, based on the in vitro degradation of DNA by bleomycin and chelated ferrous ions, it has been possible to conclude that the low molecular mass iron present in CSF is also in the reduced ferrous state. Ferrous ions are able to transfer electrons to molecular oxygen to form reactive and damaging intermediates of oxygen, some of which are free radicals. Increased levels of iron in brain tissue or CSF, however, are not necessarily synonymous with increased activation of oxygen. Detailed studies of brain iron deposits in neurological diseases are long overdue, and require new and pioneering methodologies to approach the problem.

Animals↗
PubMed1992

Vanadium and copper in clinical solutions of albumin and their potential to damage protein structure.

Solutions of albumin, for injectable use in humans, are shown to contain the transition metals vanadium, copper, and iron. Variation in the concentration of these metal ions among products from six different manufacturers suggests that problems of metal contamination arise through manufacturing processes. Vanadium concentrations correlated with the loss of tryptophan residues in albumin, whereas copper concentrations correlated with loss of thiol groups and tryptophan residues. Incubation of vanadate and cupric salts with the thiol group-containing molecules cysteine and glutathione resulted in reduction of the metal ions to lower oxidation states. Reduced forms of vanadium and copper were able to transfer electrons to molecular oxygen and produce highly reactive and damaging intermediates of oxygen, such as the hydroxyl radical.

Albumins↗
PubMed1992

Ferrous ions detected in cerebrospinal fluid by using bleomycin and DNA damage.

1. During pathological states of iron-overload or oxidant stress, low-molecular-mass iron can become available within extracellular fluids. 2. This iron would be converted to the ferrous state were it not for the protective anti-oxidant protein caeruloplasmin. 3. The ferrous-ion-oxidizing activity of caeruloplasmin rapidly converts ferrous ions back to the less reactive ferric state so that they can bind to available binding sites on transferrin. 4. Cerebrospinal fluids, however, often appear to contain low-molecular-mass iron, high levels of ascorbate and low levels of ferroxidase activity with little or no iron-binding capacity. 5. When iron ions are present in cerebrospinal fluid they are therefore likely to be in the ferrous state. 6. The development and application of an assay to speciate and measure ferrous ions in simple aqueous solution and their redox cycling activity in biological fluids is described.

Bleomycin↗
PubMed1992

Aluminium-adjuvanted vaccines transiently increase aluminium levels in murine brain tissue.

Aluminium is widely used as an adjuvant in human vaccines, and children can often receive up to 3.75 mg of parenteral aluminium during the first six months of life. We show that intraperitoneal injection of aluminium adsorbed vaccines into mice causes a transient rise in brain tissue aluminium levels peaking around the second and third day after injection. This rise is not seen in the saline control group of animals or with vaccine not containing aluminium. It is likely that aluminium is transported to the brain by the iron-binding protein transferrin and enters the brain via specific transferrin receptors.

Adjuvants, Immunologic↗
PubMed1992

Ageing and free radicals.

Mammalian ageing is a universal phenomenon that is both obvious and inevitable, yet poorly understood, and under-researched at the molecular level. Numerous ageing theories have been proposed to explain the progressive and deleterious changes characteristic of ageing. One of the most popular of these is the 'free radical' theory of ageing, which proposes that ageing results from imperfect protection against tissue damage brought about by free radicals. Oxygen free radicals are constantly produced during aerobic metabolism, and certainly provide a universal mechanism for oxidative damage. However, a major obstacle to acceptance of the theory has been the poor record of antioxidants in prolonging the lifespan of small animals. Many other variables, such as genetic factors, temperature, activity and nutrition can affect lifespan, making it a highly complex multi-factorial process.

Aged↗
PubMed1991

DNA base damage by beta-lactam, tetracycline, bacitracin and rifamycin antibacterial antibiotics.

Several antibacterial antibiotics have been shown to participate with transition metal ions in chemical reactions leading to the formation of reactive oxygen species. An important host defence mechanism for dealing with invading bacteria involves the production of reactive oxygen species, such as superoxide, hydrogen peroxide and hypochlorous acid, by phagocytic cells. The production of reactive oxygens by redox cycling antibacterial antibiotics has led us to suggest that a 'phagomimetic' contribution may also be made in vivo. Here we show that four structurally different antibacterial antibiotics, in the presence of added copper salt, bring about oxidative modification to bases in DNA detected using gas chromatography-mass spectrometry. The drug most damaging to DNA was rifamycin SV which was more active than a reference mixture of hydrogen peroxide and ascorbic acid.

Bacitracin↗
PubMed1991

Hydroxyl radical formation from the auto-reduction of a ferric citrate complex.

When a ferric citrate complex is prepared from citric acid and ferric chloride, and the pH value left unchanged, a reduction of the iron moiety takes place. Within several hours a substantial yield of ferrous ions can be detected in the solution. When placed in a phosphate buffer pH 7.0 with a suitable detector molecule, oxidative damage to the detector molecule can be observed. Thus, deoxyribose is degraded with the release of thiobarbituric acid-reactive material and benzoate is hydroxylated to form fluorescent dihydroxy products. Damage can be prevented by scavengers of the hydroxyl radical such as mannitol, formate the thiourea, by catalase and by the protein caeruloplasmin, suggesting that Fenton chemistry occurs leading to the formation of hydroxyl radicals.

Benzoates↗
PubMed1991

Plasma ascorbate levels and inhibition of the antioxidant activity of caeruloplasmin.

1. The copper-containing protein caeruloplasmin has several oxidase activities. 2. Its ability to catalyse the oxidation of ferrous ions to the ferric state (ferroxidase activity) makes it an important antioxidant in vivo. 3. Recent reports have suggested that oral supplementation with vitamin C can inhibit the oxidase activities of caeruloplasmin. 4. As expected, damage to DNA and membrane lipids was stimulated by mixtures of iron salt and ascorbate, and this damage could be inhibited by caeruloplasmin provided the molar ratio of ascorbate to caeruloplasmin was kept sufficiently low. 5. When the molar ratio of ascorbate to caeruloplasmin was greater than 200 substantial loss of ferroxidase antioxidant activity occurred. 6. It is unlikely, however, that oral supplementation with vitamin C can raise plasma levels sufficiently to inhibit caeruloplasmin activity in vivo.

Animals↗
PubMed1991

Bleomycin-detectable iron in brain tissue.

The normal brain contains regions with high concentrations of iron, part of which appears to be in a low molecular mass chelatable form. Iron complexes with a molecular mass of below 10,000, were measured in ultrafiltrates of homogenized gerbil brains using the bleomycin assay, and were found to average 20.5 +/- 3.5 microM (n = 8). As expected, no bleomycin detectable iron was found in the plasma of these animals. No obvious difference in the tissue levels of bleomycin-detectable iron was recorded following ischaemia and reperfusion. This is probably due to the already abundant presence of iron in the brain and the likely release of iron from protected sites due to structural damage inherent in the preparative procedures used.

Animals↗
PubMed1991

Superoxide-dependent reduction of some simple low molecular mass iron complexes.

Superoxide and hydrogen peroxide are often ascribed iron reducing roles in reactions leading to the formation of an aggressive oxidant by Fenton Chemistry. Hydrogen peroxide, however, does not appear to reduce iron in Fenton reactions, and we here show that several simple ferric complexes are not readily reduced to the ferrous state by superoxide generating systems. Our knowledge of low molecular mass iron complexes in vivo and their reactivity with superoxide radicals is at present insufficient for much of the chemistry proposed.

2,2'-Dipyridyl↗