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Biomedical subjects

B Halliwell

Publications and source records attributed to B Halliwell.

At least 199 records · Page 11Linked to original sources
PubMed1994

Interactions of peroxynitrite with human plasma and its constituents: oxidative damage and antioxidant depletion.

Endothelial cells and activated phagocytes produce both nitric oxide (.NO) and superoxide (O2.-), which react to form peroxynitrite. Peroxynitrite has been suggested to be directly cytotoxic and also to decompose into other toxic species. In order to understand the consequences of peroxynitrite generation in vivo, we examined its reaction with human blood plasma. Peroxynitrite decreased the total peroxyl-trapping capacity of plasma. In terms of specific antioxidants, addition of peroxynitrite to plasma leads to rapid oxidation of ascorbic acid, uric acid and plasma SH groups. The oxidation of plasma SH groups was enhanced in dialysed plasma and returned to control levels by the addition of physiological levels of bicarbonate. Evidence was found for formation of nitro-adducts to aromatic side chains in plasma proteins by peroxynitrite. Peroxynitrite also leads to depletion of ubiquinol and formation of traces of lipid hydroperoxides in plasma, although alpha-tocopherol levels were only slightly decreased. Peroxynitrite formation in human body fluids is likely to cause antioxidant depletion and oxidative damage.

Antioxidants↗
PubMed1994

Evidence for nitric oxide-mediated oxidative damage in chronic inflammation. Nitrotyrosine in serum and synovial fluid from rheumatoid patients.

Reaction of nitric oxide (NO.) with superoxide radical generates peroxy-nitrite, which can decompose to products that nitrate aromatic amino acids. Such nitro-aromatics may be 'markers' of NO.-dependent oxidative damage. Blood serum and synovial fluid from patients with the inflammatory joint disease rheumatoid arthritis contain 3-nitrotyrosine. By contrast, body fluids from normal subjects and patients with osteoarthritis contain no detectable 3-nitrotyrosine; much lower levels were found in serum from patients in the early stages of rheumatoid arthritis. This is evidence that NO. plays a role in joint damage in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1994

Aromatic hydroxylation and nitration of phenylalanine and tyrosine by peroxynitrite. Evidence for hydroxyl radical production from peroxynitrite.

Peroxynitrite is a highly reactive species, generated from superoxide and nitric oxide. Some effects of peroxynitrite are ascribed to the molecule itself, but decomposition products of the protonated form, peroxynitrous acid, may account for much of its reactivity in biological systems. Suggested products include highly-reactive hydroxyl radicals, but thermodynamic calculations have been used to claim that free hydroxyl radicals cannot be formed from peroxynitrite. We utilized aromatic hydroxylation of phenylalanine as a specific detector of hydroxyl radicals, and found that incubation of phenylalanine with peroxynitrite leads to a small amount of p-, m- and o-tyrosine, specific products of attack by this radical. Products of nitration of phenylalanine and tyrosine were also detected, as was dityrosine. Peroxynitrite decomposition generates several reactive species, including some that can nitrate aromatic rings. Formation of nitro-aromatic compounds may be a useful marker of peroxynitrite generation in biological systems.

Hydroxyl Radical↗
PubMed1994

Aromatic hydroxylation of phenylalanine as an assay for hydroxyl radicals. Measurement of hydroxyl radical formation from ozone and in blood from premature babies using improved HPLC methodology.

Highly reactive hydroxyl radicals (OH.) attack the amino acid phenylalanine to give ortho-, meta-, and para-tyrosines. An improved HPLC-based separation of these products is described. Both D- and L-phenylalanine are attacked by OH., although only the latter is a substrate for the enzyme phenylalanine hydroxylase. Use of this improved aromatic hydroxylation assay to detect OH. is illustrated by measuring OH. in ozonized aqueous solutions at pH 7.4, and by showing that blood from some premature babies appears to be capable of catalyzing OH. formation.

Catalysis↗
PubMed1994

Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxytyrosol.

Antioxidants minimize oxidation of the lipid components in foods. There is an increasing interest in the use of natural and/or synthetic antioxidants in food preservation, but it is important to evaluate such compounds fully for both antioxidant and pro-oxidant properties. The properties of thymol, carvacrol, 6-ginerol, hydroxytyrosol and zingerone were characterized in detail. Thymol, carvacrol, 6-gingerol and hydroxytyrosol decreased peroxidation of phospholipid liposomes in the presence of iron(III) and ascorbate, but zingerone had only a weak inhibitory effect on the system. The compounds were good scavengers of peroxyl radicals (CCl3O2; calculated rate constants > 10(6) M-1 sec-1) generated by pulse radiolysis. Thymol, carvacrol, 6-gingerol and zingerone were not able to accelerate DNA damage in the bleomycin-Fe(III) system. Hydroxytyrosol promoted deoxyribose damage in the deoxyribose assay and also promoted DNA damage in the bleomycin-Fe(III) system. This promotion was inhibited strongly in the deoxyribose assay by the addition of bovine serum albumin to the reaction mixtures. Our data suggest that thymol, carvacrol and 6-gingerol possess useful antioxidant properties and may become important in the search for 'natural' replacements for 'synthetic' antioxidant food additives.

Antioxidants↗
PubMed1994

Tamoxifen and related compounds protect against lipid peroxidation in isolated nuclei: relevance to the potential anticarcinogenic benefits of breast cancer prevention and therapy with tamoxifen?

Tamoxifen, 4-hydroxytamoxifen, nafoxidine, 17 beta-oestradiol and ICI 164,384 were all found to protect rat liver nuclei against Fe(III)-ascorbate dependent lipid peroxidation. The order of effectiveness of these compounds was 4-hydroxytamoxifen > 17 beta-oestradiol > nafoxidine > tamoxifen > ICI 164,384. This protection by tamoxifen against the formation of the genotoxic reactive-intermediates and products of lipid peroxidation in the nuclear membrane could be important in the prevention of nuclear DNA damage and thus carcinogenesis. This possible anticarcinogenic benefit of tamoxifen treatment could be important in long-term therapy with tamoxifen (and future derivatives) and in its proposed use in the prevention of breast cancer.

Animals↗
PubMed1994

Free radicals and antioxidants: a personal view.

Free radicals and other oxygen-derived species are constantly generated in vivo, both by "accidents of chemistry" and for specific metabolic purposes. The reactivity of different free radicals varies, but some can cause severe damage to biological molecules, especially to DNA, lipids, and proteins. Antioxidant defense systems scavenge and minimize the formation of oxygen-derived species, but they are not 100% effective. Hence, diet-derived antioxidants may be particularly important in diminishing cumulative oxidative damage and helping us to stay healthier for longer. Repair systems exist to deal with molecules that have been oxidatively damaged. Damage to DNA by hydroxyl radicals appears to occur in all aerobic cells, and might be a significant contributor to the age-dependent development of cancer. Lipid peroxidation probably contributes significantly to the development of atherosclerosis.

Antioxidants↗
PubMed1994

Oxidants, antioxidants, and respiratory tract lining fluids.

Respiratory tract lining fluids (RTLFs) are a heterogeneous group of substances covering the respiratory tract epithelial cells (RTECs) from nasal mucosa to alveoli. Antioxidant contained in the RTLFs can be expected to provide an initial defense against inhaled environmental toxins. The major antioxidants in RTLF include mucin, uric acid, protein (largely albumin), ascorbic acid, and reduced glutathione (GSH). RTLF antioxidants can be augmented by such processes as transudation/exudation of plasma constituents; RTEC secretory processes, including glandular mucus secretion; and cellular antioxidants derived from lysis of RTECs and of inflammatory cells. The antioxidant composition of RTLFs and their role in modulating normal and pathophysiologic RTEC functions under conditions of oxidative stress are yet to be fully characterized.

Animals↗
PubMed1994

Oxygen-derived species: their relation to human disease and environmental stress.

Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body, often for useful metabolic purposes. Antioxidant defenses protect against them, but these defenses are not completely adequate, and systems that repair damage by ROS are also necessary. Mild oxidative stress often induces antioxidant defense enzymes, but severe stress can cause oxidative damage to lipids, proteins, and DNA within cells, leading to such events as DNA strand breakage and disruption of calcium ion metabolism. Oxidative stress can result from exposure to toxic agents, and by the process of tissue injury itself. Ozone, oxides of nitrogen, and cigarette smoke can cause oxidative damage; but the molecular targets that they damage may not be the same.

Air Pollution↗
PubMed1994

Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation.

A detailed evaluation of the antioxidant and pro-oxidant properties of lipoic acid (LA) and dihydrolipoic acid (DHLA) was performed. Both compounds are powerful scavengers of hypochlorous acid, able to protect alpha 1-antiproteinase against inactivation by HOCl. LA was a powerful scavenger of hydroxyl radicals (OH.) and could inhibit both iron-dependent OH. generation and peroxidation of ox-brain phospholipid liposomes in the presence of FeCl3-ascorbate, presumably by binding iron ions and rendering them redox-inactive. By contrast, DHLA accelerated iron-dependent OH. generation and lipid peroxidation, probably by reducing Fe3+ to Fe2+. LA inhibited this pro-oxidant action of DHLA. However, DHLA did not accelerate DNA degradation by a ferric bleomycin complex and slightly inhibited peroxidation of arachidonic acid by the myoglobin-H2O2 system. Under certain circumstances, DHLA accelerated the loss of activity of alpha-antiproteinase exposed to ionizing radiation under a N2O/O2 atmosphere and also the loss of creatine kinase activity in human plasma exposed to gas-phase cigarette smoke. Neither LA nor DHLA reacted with superoxide radical (O.2-) or H2O2 at significant rates, but both were good scavengers of trichloromethylperoxyl radical (CCl3O2.). We conclude that LA and DHLA have powerful antioxidant properties. However, DHLA can also exert pro-oxidant properties, both by its iron ion-reducing ability and probably by its ability to generate reactive sulphur-containing radicals that can damage certain proteins, such as alpha 1-antiproteinase and creatine kinase.

Animals↗
PubMed1994

Metal ions catalytic for free radical reactions in the plasma of patients with fulminant hepatic failure.

We propose that the frequency and severity of multi-organ failure (MOF) in fulminant hepatic failure (FHF) involves free radical damage caused by the presence of circulating iron and copper ions, catalytic for free radical reactions. The presence of such metal ions is demonstrated by using the sensitive bleomycin and phenanthroline assays. Antioxidant therapy, e.g., using chelating agents that prevent metal ions from stimulating free radical reactions, may have benefit in the treatment of FHF and its consequences.

Acetaminophen↗
PubMed1994

Interactions of human blood plasma with hydrogen peroxide and hypochlorous acid.

Activated neutrophils produce both hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). Previous work has shown that HOCl depletes antioxidants, modifies proteins, and forms fatty acid chlorohydrins but does not cause significant lipid peroxidation in human plasma. Because activated phagocytes have been claimed to stimulate lipid peroxidation in plasma, we examined the effects of H2O2 and HOCl alone and in combination on plasma constituents. Hydrogen peroxide at concentrations below 0.5 mmol/L had little effect, but 1 to 2 mmol/L H2O2 caused loss of ascorbic acid and protein thiol groups, an effect potentiated by preincubation of the plasma with sodium azide to inhibit catalase. H2O2 caused no detectable lipid peroxidation or loss of alpha-tocopherol in plasma, but some depletion of ubiquinol occurred. The combination of HOCl and H2O2 caused more lipid peroxidation than either agent alone. Peroxidation was not inhibited by the metal chelators ethylenediaminetetraacetic acid and deferoxamine or by the singlet O2/hydroxyl radical scavenger histidine. We hypothesize that the phagocyte-derived H2O2 and HOCl could interact in the microenvironment of the activated leukocyte to induce lipid peroxidation of plasma lipoproteins or cell membranes (or both).

Antioxidants↗
PubMed1994

Aldehyde-induced protein modifications in human plasma: protection by glutathione and dihydrolipoic acid.

Exposure of human plasma to gas phase cigarette smoke (CS) produces a depletion of ascorbic acid, peroxidation of lipids (Frei et al. Biochem J 1991; 277: 133-8), and protein modification (as measured by protein carbonyl accumulation and loss of sulfhydryl groups) (Reznick et al. Biochem J 1992; 286: 607-11). CS contains both saturated and unsaturated aldehydes. The contribution of these aldehydes to the damaging effects of CS on human plasma was investigated. Aldehydes present in CS did not cause a depletion of plasma antioxidants such as ascorbic acid or alpha-tocopherol and did not induce plasma lipid peroxidation. Aldehydes decreased plasma protein sulfhydryl concentrations but increased protein carbonyls. The thiols glutathione and dihydrolipoic acid had a significant effect in reducing aldehyde-induced protein modifications.

Adult↗