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Epidemiologic evidence suggests that cigarette smoking is a major risk factor for chronic obstructive pulmonary diseases such as chronic bronchitis and emphysema, for carcinogenesis, and for cardiovascular disease. However, the precise mechanisms of these effects are incompletely understood. The gas phase of cigarette smoke contains abundant free radicals including nitric oxide. Hence, cigarette smoke may induce some of its damaging effects by free radical mechanisms. We report that exposure of plasma, a model for respiratory tract lining fluids, to gas-phase cigarette smoke causes depletion of antioxidants, including ascorbate, urate, ubiquinol-10, and alpha-tocopherol, and a variety of carotenoids, including beta-carotene. Gas-phase cigarette smoke induced some lipid peroxidation, as measured by cholesteryl linoleate hydroperoxide (18:2OOH) formation. Ascorbate was effective in preventing 18:2OOH formation. In contrast to the low concentrations of lipid hydroperoxides measured (< 1 mumol/L), protein carbonyl formation, a measure of protein modification, increased by approximately 400 mumol/L after nine puffs of cigarette smoke. Reduced glutathione inhibited protein carbonyl formation, whereas other plasma antioxidants, including ascorbate, were ineffective. alpha, beta-Unsaturated aldehydes (acrolein and crotonaldehyde) in cigarette smoke may react with protein -SH and -NH2 groups by a Michael addition reaction that results in a protein-bound aldehyde functional group. Gas-phase cigarette smoke is capable of converting tyrosine to 3-nitrotyrosine and dityrosine, indicating free radical mechanisms of protein damage by nitrogen oxides. Aldehydes and nitrogen oxides in cigarette smoke may be significant contributors to biomolecular damage, and endogenous antioxidants can attenuate some of these adverse effects.
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We have evaluated the abilities of ferulic acid, (±) catechin, (+) catechin and (-) epicatechin to scavenge the reactive oxygen species hydroxyl radical (OH±), hypochlorous acid (HOCl) and peroxyl radicals (RO2).Ferulic acid tested at concentrations up to 5 mM inhibited the peroxidation of phospholipid liposomes. Both (±) and (+) catechin and (-) epicatechin were much more effective. All the compounds tested reacted with trichloromethyl peroxyl radical (CCl3O2) with rate constants > 1 × 106M−1s−1.A mixture of FeCl3-EDTA, hydrogen peroxide (H2O2) and ascorbic acid at pH 7.4, has often been used to generate hydroxyl radicals (OH.) which are detected by their ability to cause damage to the sugar deoxyribose. Ferulic acid, (+) and (±) catechin and (-) epicatechin inhibited deoxyribose damage by reacting with OH. with rate constants of 4.5 × 109M−1s−1, 3.65 × 109M−1s−1, 2.36 × 109M−1s−1 and 2.84 × 109M−1s−1 respectively. (-) Epicatechin, ferulic acid and the (+) and (±) catechins exerted pro-oxidant action, accelerating damage to DNA in the presence of a bleomycin-iron complex. On a molar basis, ferulic acid was less effective in causing damage to DNA compared with the catechins.A mixture of hypoxanthine and xanthine oxidase generates O2 which reduces cytochrome c to ferrocytochrome c. (+) Catechin and (-) epicatechin inhibited the reduction of cytochrome c in a concentration dependent manner. Ferulic acid and (±) catechin had only weak effects.All the compounds tested were able to scavenge hypochlorous acid at a rate sufficient to protect alpha-1-antiproteinase against inactivation. Our results show that catechins and ferulic acid possess antioxidant properties. This may become important given the current search for "natural" replacements for synthetic antioxidant food additives.Key Words: Catechinferulic acidpro-oxidantanti-oxidantlipid peroxidationhypochlorous acid
Measurement of nitrotyrosine in biological fluids and tissues is increasingly being used to monitor the production of reactive nitrogen species in vivo. The detection of nitrotyrosine in vivo has been reported with the use of a variety of methods including immunoassay, HPLC and GLC/MS. The validity of HPLC and immunoassays have been questioned with regard to their selectivity and sensitivity limits. In principle, the measurement of nitrotyrosine by GLC/MS permits a highly specific, highly sensitive and fully quantitative assay. The nitration of tyrosine under acidic conditions in the presence of nitrite is well documented. Derivatization for the full quantification of nitrotyrosine by using GLC/MS can lead to the artifactual nitration of tyrosine if performed under acidic conditions in the presence of nitrite. We describe a novel alkaline method for the hydrolysis and derivatization of nitrotyrosine and tyrosine, and demonstrate its applicability to the measurement of plasma concentrations of both free and protein-bound nitrotyrosine and tyrosine. A detection limit of 1 pg for nitrotyrosine and 100 pg for tyrosine has been achieved. Our method allows, for the first time, the analysis of free and protein-bound nitrotyrosine and tyrosine in biological samples. The plasma concentrations (means±S.E.M.) of free tyrosine and nitrotyrosine in eight normal subjects were 12±0.6 μg/ml and 14±0.7 ng/ml respectively. Plasma proteins contained tyrosine and nitrotyrosine at 60.7±1.7 μg/mg and 2.7±0.4 ng/mg respectively.
The basic chemistry of the propagation of lipid peroxidation reactions has been known for years, but the mechanism of initiation of this process in biological membrane systems is still uncertain. Currently available assays for measuring peroxidation are reviewed - the more specific the assay used, the less peroxide is found in healthy human tissues and body fluids. Lipid peroxidation can arise as a consequence of tissue injury in many disease states and may sometimes contribute significantly to worsening the tissue injury.
Background and Purpose— We observed recently that elevated plasma cysteine levels are associated with poor clinical outcome in acute stroke patients. In a rat stroke model, cysteine administration increased the infarct volume apparently via its conversion to hydrogen sulfide (H 2 S). We therefore investigated the effects of H 2 S and the inhibition of its formation on stroke. Methods— Cerebral ischemia was studied in a rat stroke model created by permanent occlusion of the middle cerebral artery (MCAO). The resultant infarct volume was measured 24 hours after occlusion. Results— Administration of sodium hydrosulfide (NaHS, an H 2 S donor) significantly increased the infarct volume after MCAO. The NaHS-induced increase in infarct volume was abolished by the administration of dizolcilpine maleate (an N -methyl- d -aspartate receptor channel blocker). MCAO caused an increase in H 2 S level in the lesioned cortex as well as an increase in the H 2 S synthesizing activity. Administration of 4 different inhibitors of H 2 S synthesis reduced MCAO-induced infarct volume dose dependently. The potency of these inhibitors in effecting neuroprotection in vivo appeared to parallel their potency as inhibitors of H 2 S synthesis in vitro. It also appeared that most of the H 2 S synthesizing activity in the cortex results from the action of cystathionine β-synthase. Conclusions— The present results strongly suggest that H 2 S plays a part in cerebral ischemic damage after stroke. Inhibition of H 2 S synthesis should be investigated for its potential as a novel neuroprotective stroke therapy.
This chapter defines the terms oxidative stress and oxidative damage, and explains how they can affect cell behaviour: proliferation, adaptation, injury, senescence, intercellular communication, and cell death by apoptosis, necrosis, parthanatos (activation of poly-ADP ribose polymerase), and other mechanisms such as pyroptosis. The role played by reactive species (RS) in apoptosis is detailed. The effects of reactive species (RS) on ion channels and ion levels are presented, especially for K+, Ca2+, iron ions, and copper ions. Methods to measure the liberalization of 'catalytic' iron and copper ions by oxidative stress are described. There is a detailed description of the mechanisms by which RS (including hydroxyl radicals, singlet oxygen, hypochlorous acid, and peroxynitrite) cause damage to DNA, how this can lead to mutations, and how cells counter this by repair mechanisms. The ways in which defects in DNA repair raise the risk of cancer development in diseases, such as xeroderma pigmentosum, Lynch syndrome, ataxia telangiectasia, and Cockayne syndrome are presented. Oxidative protein damage and lipid peroxidation are explored in detail, including the mechanisms that cells have evolved to deal with them. The cellular actions of end-products of lipid peroxidation (isoprostanes, aldehydes, cholesterol oxidation products etc.) are reviewed. Heat-shock proteins, the acute phase response, the proteasome, and autophagy are described in detail. Redox regulation in bacterial, yeast and animal cells is reviewed in detail, and its physiological relevance discussed, especially for kinases, phosphatases (including PTEN), Nrf2, NF-κB (particularly the role of ROS in regulating its activity), AP-1, and mitochondria-to-nucleus signalling.
The chloroplasts in the leaves of higher plants produce several damaging oxygen-derived species in the light, namely, hydrogen peroxide, singlet oxygen, lipid peroxides, superoxide, and the hydroxyl radical. The high concentration of ascorbic acid often present in the chloroplast helps to protect them against these species.
Research Article| April 01 1984 Oxygen toxicity, oxygen radicals, transition metals and disease B Halliwell; B Halliwell Search for other works by this author on: This Site PubMed Google Scholar J M C Gutteridge J M C Gutteridge Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1984) 219 (1): 1–14. https://doi.org/10.1042/bj2190001 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Cite Icon Cite Get Permissions Citation B Halliwell, J M C Gutteridge; Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 1 April 1984; 219 (1): 1–14. doi: https://doi.org/10.1042/bj2190001 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1984 London: The Biochemical Society1984 Article PDF first page preview Close Modal You do not currently have access to this content.
