Summary
A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology of more than 50 human diseases. Radicals and other reactive oxygen species are formed constantly in the human body, both by deliberate synthesis (e.g. by activated phagocytes) and by chemical side- reactions. They are removed by enzymic and nonenzymic antioxidant defence systems. Oxidative stress, occurring when antioxidant defences are inadequate, can damage lipids, proteins, carbohydrates and DNA. A few clinical conditions are caused by oxidative stress, but more often the stress results from the disease. Sometimes it then makes a significant contribution to the disease pathology, and sometimes it does not. Several antioxidants are available for therapeutic use. They include molecules naturally present in the body [superoxide dismutase (SOD), α-tocopherol, glutathione and its precursors, ascorbic acid, adenosine, lactoferrin and carotenoids] as well as synthetic antioxidants [such as thiols, ebselen (PZ51), xanthine oxidase inhibitors, inhibitors of phagocyte function, iron ion chelators and probucol]. The therapeutic efficacy of SOD, α- tocopherol and ascorbic acid in the treatment of human disease is generally unimpressive to date although dietary deficiencies of the last two molecules should certainly be avoided. Xanthine oxidase inhibitors may be of limited relevance as antioxidants for human use. Exciting preliminary results with probucol (antiatherosclerosis), ebselen (anti-inflammatory), and iron ion chelators (in thalassaemia, leukaemia, malaria, stroke, traumatic brain injury and haemorrhagic shock) need to be confirmed by controlled clinical trials. Clinical testing of N-acetylcysteine in HIV-1-positive subjects may also be merited. A few drugs already in clinical use may have some antioxidant properties, but this ability is not widespread and drug- derived radicals may occasionally cause significant damage.
Article PDF
Similar content being viewed by others
References
Ahnfelt-Ronne I, Nielsen OH, Christensen A, Longholz E, Binder V, et al. Clinical evidence supporting the radical scavenger mechanism of 5-aminosalicylic acid. Gastroenterology 98: 1162–1169, 1990
Aitken RJ. The role of free oxygen radicals and sperm function. International Journal of Andrology 12: 95–97, 1989
Akaike T, Ando M, Oda T, Doi T, Ijiri S, et al. Dependence on O2-generation by xanthine oxidase of pathogenesis of influenza virus infection in mice. Journal of Clinical Investigation 85: 739–745, 1990
Albano E, Bellomo G, Paiola M, Carini R, Dianzani MU. Stimulation of lipid peroxidation increases the intracellular calcium content of isolated hepatocytes. Biochimica et Biophysica Acta 1091: 310–316, 1991
Allan G, Cambridge D, Lee-Tsang-Tan L, Van Way CW, Whiting MV. The protective action of allopurinol in an experimental model of haemorrhagic shock and reperfusion. British Journal of Pharmacology 89: 149–155, 1986
Ambrosio G, Becker LC, Hutchins GM, Weisman HF, Weisfeldt ML. Reduction in experimental infarct size by recombinant human Superoxide dismutase: insights into the pathophysiology of repeffusion injury. Circulation 74: 1424–1433, 1986
Ames BN, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant-and radical-causing aging and cancer: a hypothesis. Proceedings of the National Academy of Sciences of the USA 78: 6858–6862, 1981
Anderson ME, Meister A. Glutathione monoesters. Analytical Biochemistry 183: 16–20, 1989a
Anderson ME, Meister A. Marked increase of cysteine levels in many regions of the brain after administration of 2-oxothia-zolidine-4-carboxylate. FASEB Journal 3: 1632–1636, 1989b
Arroyo CM, Carmichael AJ, Bouscarel B, Liang JH, Weglicki WB. Endothelial cells as a source of oxygen free radicals: an ESR study. Free Radical Research Communications 9: 287–296, 1990
Artuso T, Bernadon J, Meunier B, Paillous N. DNA strand breaks photosensitized by benoxaprofen and other non-steroidal anti-inflammatory agents. Biochemical Pharmacology 39: 407–413, 1990
Aruoma CI, Akanmu D, Cecchini R, Halliwell B. Evaluation of the ability of the angiotensin-converting enzyme inhibitor captopril to scavenge reactive oxygen species. Chemico-Biological Interactions 77: 363–314, 1991b
Aruoma OI, Halliwell B. Superoxide-dependent and ascorbate-dependent formation of hydroxyl radicals from hydrogen peroxide in the presence of iron. Biochemical Journal 241: 273–278, 1987
Aruoma OI, Wasil M, Halliwell B, Hoey BM, Butler J. The scavenging of oxidants by sulphasalazine and its metabolites. Biochemical Pharmacology 36: 3739–3742, 1987
Aruoma OI, Halliwell B, Dizdaroglu M. Iron ion-dependent modification of bases in DNA by the Superoxide radical-generating system hypoxanthine/xanthine oxidase. Journal of Biological Chemistry 264: 13024–13028, 1989a
Aruoma OI, Halliwell B, Laughton MJ, Quinlan GJ, Gutteridge JMC. The mechanism of initiation of lipid peroxidation. Biochemical Journal 258: 617–620, 1989b
Aruoma OI, Halliwell B, Butler J, Hoey BM. Apparent inactivation of α1-antiproteinase by sulphur-containing radicals derived from penicillamine. Biochemical Pharmacology 38: 4353–4357, 1989c
Aruoma OI, Evans PJ, Kaur H, Sutcliffe L, Halliwell B. An evaluation of the antioxidant and potential pro-oxidant properties of food additives and of Trolox C, vitamin E and probucol. Free Radical Research Communications 10: 143–157, 1990
Aruoma OI, Halliwell B, Gajewski E, Dizdaroglu M. Copper-iondependent damage to the bases in DNA in the presence of hydrogen peroxide. Biochemical Journal, in press, 1991a
Ash D, Brown SB. Photodynamic therapy-achievements and prospects. British Journal of Cancer 60: 151–152, 1989
Baader WJ, Hatzelmann A, Ullrich V. The suppression of granulocyte functions by lipophilic antioxidants. Biochemical Pharmacology 37: 1089–1098, 1988
Bagchi D, Iyengar J, Stockwell P, Das DK. Enhanced prostaglandin production in the ischemic-reperfused myocardium by captopril linked with its free radical scavenging action. Prostaglandins, Leukotrienes and Essential Fatty Acids 38: 145–150, 1989
Ball RY, Carpenter KLH, Mitchinson MJ. What is the significance of ceroid in human atherosclerosis? Archives of Pathology and Laboratory Medicine 111: 1134–1140, 1987
Baruchel S, Gao Q, Wainberg MA. Desferrioxamine and HIV. Lancet 337: 1356, 1991
Beck Y, Bartfield D, Yavin Z, Levanon A, Gorecki M, et al. Efficient production of active human manganese Superoxide dis-mutase in Escherichia coll. Biotechnology 6: 930–935, 1988
Beckman JS. Ischaemic injury mediator. Nature 345: 27–28, 1990
Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proceedings of the National Academy of Sciences of the USA 87: 1620–1624, 1990
Bell D, Jackson M, Nicoll JJ, Millar A, Dawes J, et al. Inflammatory response, neutrophil activation, and free radical production after acute myocardial infarction: effect of thrombolytic treatment. British Heart Journal 63: 82–87, 1990
Bendich A, Olson JA. Biological actions of carotenoids. FASEB Journal 3: 1927–1932, 1989
Bendich A, Machlin LJ, Scandurra O, Burton GW, Wayner DDM. The antioxidant role of vitamin C. Advances in Free Radical Biology and Medicine 2: 419–444, 1986
Bendich A, Machlin LJ. Safety of oral intake of vitamin E. American Journal of Clinical Nutrition 48: 612–619, 1988
Beyer Jr WF, Fridovich I. Characterization of a Superoxide dismutase mimic prepared from desferrioxamine and Mn O2. Archives of Biochemistry and Biophysics 271: 149–156, 1989
Biemond P, Van Eijk HG, Swaak AJG, Koster JF. Iron mobilization from ferritin by Superoxide derived from stimulated polymorphonuclear leukocytes: possible mechanism in inflammation diseases. Journal of Clinical Investigation 73: 1576–1579, 1984
Bieri JG, Corash L, Van Hubbard S. Medical uses of vitamin E. New England Journal of Medicine 308: 1063–1071, 1983
Bierer BE, Nathan DG. The effect of desferrithiocin, an oral iron chelator, on T-cell function. Blood 76: 2052–2059, 1990
Birgens HS. The biological significance of lactoferrin in haematology. Scandinavian Journal of Haematology 33: 225–230, 1984
Blake DR, Winyard P, Lunec J, Williams A, Good P, et al. Cerebral and ocular toxicity induced by desferrioxamine. Quarterly Journal of Medicine 219: 345–355, 1985
Bolann BJ, Ulvik RJ. On the limited ability of Superoxide to release iron from ferritin. European Journal of Biochemistry 193: 899–904,1990
Bolli R. Oxygen-derived free radicals and postischemic myocardial dysfunction (’stunned myocardium’). Journal of the American College of Cardiology 12: 239–249, 1988
Bolli R. Superoxide dismutase ten years later: a drug in search of a use. Journal of the American College of Cardiology 18: 231–233, 1991
Bolli R, Jerudi MO, Patel BS, Aruoma OI, Halliwell B, et al. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Circulation Research 65: 607–622, 1989
Bolli R, Patel BS, Jeroudi MO, Li XY, Triana JF, et al. Iron-mediated radical reactions upon reperfusion contribute to myocardial stunning. American Journal of Physiology 259: H1901–H1911, 1990
Bonomi F, Cerioli A, Pagani S. Molecular aspects of the removal of ferritin-bound iron by DL-dihydrolipoate. Biochimica et Biophysica Acta 994: 180–186, 1989
Boudjema K, Van Gulik TM, Lindell SL, Vieugdenhil PS, Southard JH, et al. Effect of oxidized and reduced glutathione in liver preservation. Transplantation 50: 948–951, 1990
Bradley B, Prowse SJ, Bauling P, Lafferty EJ. Desferrioxamine treatment prevents chronic islet allograft damage. Diabetes 35: 550–555, 1986
Breimer LH. Ionizing radiation-induced mutagenesis. British Journal of Cancer 57: 6–18, 1988
Bruckdorfer KR, Jacobs M, Rice-Evans C. Endothelium-derived relaxing factor (nitric oxide) lipoprotein oxidation and atherosclerosis. Biochemical Society Transactions 18: 1061–1063, 1990
Buhl R, Jaffe HA, Holroyd KJ, Wells FB, Mastrangeli A, et al. Systemic glutathione deficiency in symptom-free HIV-seropositive patients. Lancet 2: 1294–1296, 1989
Buhl R, Vogelmeier C, Critenden M, Hubbard RC, Hoyt Jr RF, et al. Augmentation of glutathione in the fluid lining the epithelium of the lower respiratory tract by directly administering glutathione aerosol. Proceedings of the National Academy of Sciences of the USA 87: 4063–4067, 1990
Burdon RH, Rice-Evans CRE. Free radicals and the regulation of mammalian cell proliferation. Free Radical Research Communications 6: 345–358, 1989
Burton GW, Wronska U, Stone L, Foster DO, Ingold KU. Biok-inetics of dietary RRR-α-tocopherol in the male guinea pig at three dietary levels of vitamin C and two levels of vitamin E: evidence that vitamin C does not “spare” vitamin E in vivo Lipids 25: 199–210, 1990
Cameron E, Campbell A. The orthomolecular treatment of cancer. Chemico-Biological Interactions 9: 285–315, 1974
Cantin AM, North SL, Hubbard RC, Crystal RG. Normal alveolar epithelial lining fluid contains high levels of glutathione. Journal of Applied Physiology 63: 152–157, 1987
Carden DL, Smith JK, Zimmerman BJ, Korthuis RJ, Granger DN. Reperfusion injury following circulatory collapse: the role of reactive oxygen metabolites. Journal of Critical Care 4: 294–307, 1989
Carew TE, Schwenke DC, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolaemic effect: evidence that antioxidants in vivo can selectively inhibit LDL degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proceedings of the National Academy of Sciences of the USA 84: 7725–7729, 1987
Carini R, Poli G, Dianzani MU, Maddix SP, Slater TF, et al. Comparative evaluation of the antioxidant properties of α-tocopherol, α-tocopherol polyethylene glycol 1000 succinate and α-tocopherol succinate in isolated hepatocytes and liver microsomal suspensions. Biochemical Pharmacology 39: 1597–1601, 1990
Chalmers RA, Kromer H, Scott JT, Walt RWE. A comparative study of the xanthine oxidase inhibitors àllopurinol and oxypurinol in man. Clinical Science 35: 353–362, 1968
Chambers DJ, Braimbridge MV, Hearse DJ. Free radicals and cardioplegia: allopurinol and oxypurinol reduce myocardial injury following ischemic arrest. Annals of Thoracic Surgery 44: 291–297, 1987
Chiswick M, Gladman G, Sinha S, Toner N, Davies J. Vitamin E supplementation and peri ventricular hemorrhage in the newborn. American Journal of Clinical Nutrition 53: 370S–372S, 1991
Chow CK, Thacker RR, Changchit C, Bridges RB, Rehm SR, et al. Lower levels of vitamin C and carotenes in plasma of cigarette smokers. Journal of the American College of Nutrition 5: 305–312, 1986
Clark IA, Hunt WH, Cowden WB. Oxygen-derived free radicals in the pathogenesis of parasitic disease. Advances in Parasitology 25: 1–44, 1986
Claxson A, Morris C, Blake D, Siren M, Halliwell B, et al. The anti-inflammatory effects of D-myo-inositol-l,2,6-triphosphate (PP56) on animal models of inflammation. Agents and Actions 29: 67–70, 1990
Cohen MV. Free radicals in ischemic and reperfusion myocardial injury: is this the time for clinical trials? Annals of Internal Medicine 111: 918–931, 1989
Corash L, Spielberg S, Bartsocas C, Boxer L, Steinherz R, et al. Reduced chronic hemolysis during high-dose vitamin E administration in Mediterranean-type glucose-6-phosphate dehydrogenase deficiency. New England Journal of Medicine 303: 416–420, 1980
Cotgreave IA, Duddy SK, Kass GEN, Thompson D, Moldeus P. Studies on the anti-inflammatory activity of Ebselen. Biochemical Pharmacology 38: 649–656, 1989
Cronstein BN, Daguma L, Nichols D, Hutchison AJ, Williams M. The adenosine/neutrophil paradox resolved: human neutrophils possess both A1and A2receptors that promote chemotaxis and inhibit O2- generation, respectively. Journal of Clinical Investigation 85: 1150–1157, 1990
Cross AR. Inhibitors of the leukocyte Superoxide generating oxidase. Free Radical Biology and Medicine 8: 71–93, 1990
Cross CE, Forte T, Stocker R, Louie S, Yamamoto Y, et al. Oxidative stress and abnormal cholesterol metabolism in patients with adult respiratory distress syndrome. Journal of Laboratory and Clinical Medicine 115: 396–404, 1990
Curnutte JT, Babior BM. Chronic granulomatous disease. Advances in Human Genetics 16: 229–245, 1987
Currin RT, Toole JG, Thurman RG, Lemasters JJ. Evidence that Carolina rinse solution protects sinusoidal endothelial cells against reperfusion injury after cold ischemic storage of rat liver. Transplantation 50: 1076–1078, 1990
Curzio M. Interaction between neutrophils and 4-hydroxyalkenals and consequences on neutrophil mobility. Free Radical Research Communications 5: 55–66, 1988
Davies MJ. Detection of myoglobin-derived radicals on reaction of metmyoglobin with hydrogen peroxide and other peroxidic compounds. Free Radical Research Communications 10: 361–370, 1990
Davis S.C, Marcus RE, Hungerford JL, Miller MH, Arden GB, et al. Ocular toxicity of high-dose intravenous desferrioxamine. Lancet 1: 181–184, 1983
Davison A, Tibbits G, Shi Z, Moon J. Active oxygen in neuro-muscular disorders. Molecular and Cellular Biochemistry 84: 199–216, 1988
Dean RT, Thomas SM, Garner A. Free radical-mediated fragmentation of monoamine oxidase in the mitochondrial membrane: role of lipid radicals. Biochemical Journal 240: 489–494, 1986
Del Nido PJ, Mickle DAG, Wilson GJ, Benson LN, Coles JG, et al. Evidence of myocardial free radical injury during elective repair of tetralogy of Fallot. Circulation 76 (Suppl. V): V-174–V-179, 1987
Diplock AT. Fat-soluble vitamins, their biochemistry and applications, pp. 154–224, Heinemann, London, 1985
Dobbin PS, Hider RC. Iron cheiation therapy. Chemistry in Britain 565-568, 1990
Docampo R. Sensitivity of parasites to free radical damage by antiparasitic drugs. Chemico-Biological Interactions 73: 1–27, 1990
Donatus IA, Sardjoko, Vermeulen NPE. Cytotoxic and cytoprotective activities of curcumin. Biochemical Pharmacology 39: 1869–1875, 1990
Downey JM, Omar B, Ooiwa H, McCord J. Superoxide dismutase therapy for myocardial ischaemia. Free Radical Research Communications 12: 703–720, 1991
Editorial. Reperfusion injury after thrombolytic therapy for acute myocardial infarction. Lancet 2: 655-657, 1989a
Editorial. Oral iron chelators. Lancet 2: 1016-1017, 1989b
Ehrenkranz RA. Vitamin E and retinopathy of prematurity: still controversial. Journal of Pediatrics 114: 801–803, 1989
El-Hage AH, Herman EH, Ferrans VJ. Reduction in the diabetogenic effect of alloxan in mice by treatment with the anti-neoplastic agent ICRF-187. Research Communications in Chemical Pathology and Pharmacology 33: 509–523, 1981
Engle WA, Yoder MC, Baurley JL, Yu PL. Vitamin E decreases Superoxide anion production by polymorphonuclear leukocytes. Pediatric Research 23: 245–248, 1988
Engler R. Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia. Federation Proceedings 46: 2407–2412, 1987
Engler R, Gilpin E. Can Superoxide disniutase alter myocardial infarct size? Circulation 79: 1137–1142, 1989
Epstein JH. Chemical phototoxicity in humans. Journal of the National Cancer Institute 69: 265–268, 1982
Esterbauer H, Zollner H, Schaur RJ. Hydroxyalkenals: cytotoxic products of lipid peroxidation. ISI Atlas of Science, Biochemistry 1: 311–315, 1988
Esterbauer H, Striegl G, Puhl H, Rotheneder M. Continuous monitoring of in vitrooxidation of human low density lipoprotein. Free Radical Research Communications 6: 67–75, 1989
Estrov Z, Cohen A, Gelfand EW, Freedman MH. In vitrocytotoxicity of deferoxamine on human bone marrow haematopoietic progenitors. Toxicology In Vitro 2: 131–134, 1988
Fariss MW. Oxygen toxicity: unique cytoprotective properties of vitamin E succinate in hepatocytes. Free Radical Biology and Medicine 9: 333–343, 1990
Fariss MW, Merson MH, O’Hara TM. a-Tocopheryl succinate protects hepatocytes from chemical-induced toxicity under physiological calcium conditions. Toxicology Letters 47: 61–75, 1989
Fischer H, Terlinden R, Löhr JP, Römer A. A novel biologically active selenoorganic compound VIII: biotransformation of Eb-selen. Xenobiotica 18: 1347–1359, 1988
Ferrari R, Alfieri O, Curello S, Ceconi C, Cargnoni A, et al. Occurrence of oxidative stress during reperfusion of the human heart. Circulation 81: 201–211, 1990
Flint DH, Emptage MH. A new mode of action for Superoxide: inactivation of enzymes with [Fe-S] clusters. Free Radical Research Communications, in press, 1991
Flohé L. Superoxide dismutase for therapeutic use: clinical experience, dead ends and hopes. Molecular and Cellular Biochemistry 84: 123–131, 1988
Forman MB, Puett DW, Virmiani R. Endothelial and myocardial injury during ischemia and reperfusion: pathogenesis and therapeutic implications. Journal of the American College of Cardiology 13: 450–459, 1989
Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proceedings of the National Academy of Sciences of the USA 86: 6377–6381, 1989
Fridovich I. Superoxide radical, an endogenous toxicant. Annual Review of Pharmacology and Toxicology 23: 239–257, 1983
Friedl HP, Smith DJ, Till GO, Thomson PD, Louis DS, et al. Ischemia-reperfusion in humans. Appearance of xanthine oxidase activity. American Journal of Pathology 136: 491–495, 1990
Friedman HS, Colvin OM, Aisaka K, Popp J, Bossen EH, et al. Glutathione protects cardiac and skeletal muscle from cyclophosphamide-induced injury. Cancer Research 50: 2455–2462, 1990
Fuller BJ, Gower JD, Green CJ. Free radical damage and organ preservation: fact or fiction? Cryobiology 25: 377–393, 1988
Galaris D, Mira D, Sevanian A, Cadenas E, Hochstein P. Co-oxidation of salicylate and cholesterol during the oxidation of metmyoglobin by H2O2. Archives of Biochemistry and Biophysics 262: 221–231, 1988
Gey KF. The antioxidant hypothesis of cardiovascular disease: epidemiology and mechanisms. Biochemical Society Transactions 18: 1041–1045, 1990
Gey KF, Brubacher GB, Stahelin HB. Plasma levels of antioxidant vitamins in relation to ischaemic heart disease and cancer. American Journal of Clinical Nutrition 45: 1368–1377, 1987
Giri SN, Hyde DM, Schiedt MJ. Effects of repeated administration of N-acetyl-L-cysteine on sulfhydryl levels of different tissues and bleomycin-induced lung fibrosis in hamsters. Journal of Laboratory and Clinical Medicine 111: 715–724, 1988
Gower JD, Healing G, Fuller BJ, Simpkin S, Green CJ. Protection against oxidative damage in cold-stored rabbit kidneys by desferrioxamine and indomethacin. Cryobiology 26: 309–317, 1989b
Gower J, Healing G, Green C. Measurement by HPLC of desferrioxamine-available iron in rabbit kidneys to assess the effect of ischaemia on the distribution of iron within the total pool. Free Radical Research Communications 5: 291–299, 1989a
Grady RW, Graziano JH, White GP, Jacobs A, Cerami A. The development of new iron-chelating drugs II. Journal of Pharmacology and Experimental Therapeutics 205: 757–765, 1978
Graf E, Eaton JW. Antioxidant functions of phytic acid. Free Radical Biology and Medicine 8: 61–69, 1990
Greenwald RA. Superoxide dismutase and catalase as therapeutic agents for human diseases: a critical review. Free Radical Biology and Medicine 8: 201–209, 1990
Greenwald RA. Therapeutic usages of oxygen radical scavengers in human diseases: myths and realities. Free Radical Research Communications 12: 531–538, 1991
Grisham MB, Hernandez LA, Granger DN. Adenosine inhibits ischemia-reperfusion-induced leukocyte adherence and extravasation. American Journal of Physiology 257: H1334–H1339, 1989
Grootveld M, Halliwell B, Moorhouse CP. Action of uric acid, allopurinol and oxypurinol on the myeloperoxidase-derived oxidant hypochlorous acid. Free Radical Research Communications 4: 69–76, 1987
Gutteridge JMC. Iron promoters of the Fenton reaction and lipid peroxidation can be released from haemoglobin by peroxides. FEBS Letters 201: 291–295, 1986
Gutteridge JMC. Bleomycin-detectable iron in knee-joint synovial fluid from arthritic patients and its relationship to the extracellular antioxidant activities of caeruloplasmin, transferrin and lactoferrin. Biochemical Journal 245: 415–421, 1987
Gutteridge JMC, Smith A. Antioxidant protection by haemopexin of haem-stimulated lipid peroxidation. Biochemical Journal 256: 861–865, 1988
Gutteridge JMC, Stocks J. Ceruloplasmin: physiological and pathological perspectives. CRC Critical Reviews in Clinical Laboratory Science 14: 257–329, 1981
Gutteridge JMC, Xaio-Chang F. Enhancement of bleomycin-iron free radical damage to DNA by antioxidants and their inhibition of lipid peroxidation. FEBS Letters 123: 71–74, 1981
Gutteridge JMC, Richmond R, Halliwell B. Inhibition of the iron-catalyzed formation of hydroxyl radicals from Superoxide and of lipid peroxidation by desferrioxamine. Biochemical Journal 184: 469–472, 1979
Gutteridge JMC, Paterson SK, Segal AW, Halliwell B. Inhibition of lipid peroxidation by the iron-binding protein lactoferrin. Biochemical Journal 199: 259–261, 1981
Gutteridge JMC, Rowley DA, Griffiths E, Halliwell B. Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. Clinical Science 68: 463–467, 1985
Haenen GRMM, Vermeulen NPE, Timmerman H, Bast A. Effect of thiols on lipid peroxidation in rat liver microsomes. Chemico-Biological Interactions 71: 201–212, 1989
Hall ED, Braughler JM. Central nervous system trauma and stroke. Free Radical Biology and Medicine 6: 303–313, 1989
Hallaway PE, Eaton JW, Panter SS, Hedlund BE. Modulation of deferoxamine toxicity and clearance by covalent attachment to biocompatible polymers. Proceedings of the National Academy of Sciences of the USA 86: 10108–10112, 1989
Halliwell B. Oxidants and human disease: some new concepts. FASEB Journal 1: 358–364, 1987
Halliwell B. Albumin, an important extracellular antioxidant? Biochemical Pharmacology 37: 569–571, 1988
Halliwell B. Superoxide, iron, vascular endothelium and reperfusion injury. Free Radical Research Communications 5: 315–318, 1989a
Halliwell B. Oxidants and the central nervous system: some fundamental questions. Acta Neurologica Scandinavica 126: 23–33, 1989b
Halliwell B. Free radicals, reactive oxygen species and human disease: a critical evaluation with special reference to atherosclerosis. British Journal of Experimental Pathology 70: 737–757, 1989c
Halliwell B. Protection against tissue damage in vivo by desferrioxamine: what is its mechanism of action? Free Radical Biology and Medicine 7: 645–651, 1989d
Halliwell B. How to characterize a biological antioxidant. Free Radical Research Communications 9: 1–36, 1990
Halliwell B, Aruoma OI. DNA damage by oxygen-derived species: Its mechanism and measurement in mammalian systems. FEBS Letters 281: 9–19, 1991
Halliwell B, Bomford A. ICRF-187 and doxorubicin-induced cardiac toxicity. New England Journal of Medicine 320: 399–400, 1989
Halliwell B, Cross GE. Reactive oxygen species, antioxidants and acquired immunodeficiency syndrome. Sense or speculation? Archives of Internal Medicine 151: 29–31, 1991
Halliwell B, Grootveld M. The measurement of free radical reactions in humans. FEBS Letters 213: 9–14, 1987
Halliwell B, Gutteridge JMC. Lipid peroxidation, oxygen radicals, cell damage and antioxidant therapy. Lancet 1: 1396–1398, 1984
Halliwell B, Gutteridge JMC. Oxygen radicals and the nervous system. Trends in Neuroscience 8: 22–26, 1985
Halliwell B, Gutteridge JMC. Free radicals in biology and medicine, 2nd ed., Clarendon Press, Oxford, 1989
Halliwell B, Gutteridge JMC. Role of free radicals and catalytic metal ions in human disease: an overview. Methods in Enzymology 186: 1–86, 1990a
Halliwell B, Gutteridge JMC. The antioxidants of extracellular fluids. Archives of Biochemistry and Biophysics, 280: 1–8,1990b
Halliwell B, Gutteridge JMC, Blake D. Metal ions and oxygen radical reactions in human inflammatory joint disease. Philosophical Transactions of the Royal Society, series B 311: 659–671, 1985
Halliwell B, Hoult JRS, Blake DR. Oxidants, inflammation and anti-inflammatory drugs. FASEB Journal 2: 501–514, 1988a
Halliwell B, Aruoma OI, Mufti G, Bomford A. Bleomycin-detectable iron in serum from leukaemicj patients before and after chemotherapy. FEBS Letters 241: 202–204, 1988b
Hart BAT, Simons JM, Knaan-Shanzer S, Bakker NPM, Labadie RP. Antiarthritic activity of the newly developed neutrophil oxidative burst antagonist apocynin. IFree Radical Biology and Medicine 9: 127–131, 1990
Hayashi M, Slater TF. Inhibitory effects of Ebselen on lipid peroxidation in rat liver microsomes. Free Radical Research Communications 2: 179–185, 1986
Heffner JE, Repine JE. Pulmonary strategies of antioxidant defense. American Review of Respiratory Disease 140: 531–554, 1989
Held KD. Models for thiol protection of DNA in cells. Pharmacology and Therapeutics 39: 123–131, 1988
Heppner DG, Hallaway PE, Kontoghiorghes GJ, Eaton JW. Antimalarial properties of orally active iron chelators. Blood 72: 358–361, 1988
Hermens WT, Willems GM, van der Vusse GJ. Minimal myocardial injury after uncomplicated coronary bypass surgery: various sources of overestimation. Clinica Chimica Acta 173: 243–250, 1988
Hershko C. Oral iron chelating drugs: coming but not yet ready for clinical use. British Medical Journal 296: 1081, 1988
Hershko C, Peto TEA. Deferoxamine inhibition of malaria is independent of host iron status. Journal of Experimental Medicine 168: 375–387, 1988
Hershko C, Theanacho EN, Spira DT, Peter HH, Dobbin P, et al. The effect of N-alkyl modification on the antimalarial activity of 5-hydroxypyridin-4-one oral iron chelators. Blood 77: 637–643, 1991
Hill HAO. Oxygen, oxidases and the essential trace metals. Philosophical Transactions of the Royal Society of London B294: 119–128, 1981
Hodnick WF, Kung FS, Roettger WJ, Bohmont CW, Pardini RS. Inhibition of mitochondrial respiration and production of toxic oxygen radicals by flavonoids. Biochemical Pharmacology 35: 2345–2357, 1986
Howard LJ. The neurologic syndrome of vitamin E deficiency: laboratory and electrophysiological assessment. Nutrition Reviews 48: 169–177, 1990
Huang L, Privalle CT, Serafin D, Klitzman B. Increased survival of skin flaps by scavengers of Superoxide radical. FASEB Journal 1: 129–132, 1987
Hunt WH, Stocker R. Oxidative stress and the redox status of malaria-infected erythrocytes. Blood Cells 16: 499–526, 1990
Imlay JA. Fridovich I. Assays of metabolic Superoxide production in Escherichia coli. Journal of Biological Chemistry 266: 6957–6965, 1991
Imlay JA, Linn S. DNA damage and oxygen radical toxicity. Science 240: 1302–1309, 1988
Ingold KU, Burton GW, Foster DO, Zucker M, Hughes L, et al. A new vitamin E analogue more active than α-tocopherol in the rat curative myopathy bioassay. FEBS Letters 205: 117–120, 1986
Ingold KU, Burton GW, Foster DO, Hughes L. Further studies of a new vitamin E analogue more active than α-tocopherol in the rat curative myopathy bioassay. FEBS Letters 267: 63–65, 1990
Inoue M, Watanabe N, Morino Y, Tanaka Y, Amachi T, et al. Inhibition of oxygen toxicity by targeting Superoxide dismutase to endothelial cell surface. FEBS Letters 269: 89–92, 1990
Issels RD, Bourier S, Boning B, Li GC, Mak JJ, et al. Influence of oxidative stress induced by cysteamine upon the induction and development of thermotolerance in Chinese Hamster ovary cells. Cancer Research 47: 2268–2274, 1987
Itoh T, Kawamaki M, Yamauchi Y, Shimizu S, Nakamura M. Effect of allopurinol on ischemia and reperfusion-induced cerebral injury in spontaneously hypertensive rats. Stroke 17: 1284–1287, 1986
Jacobsen EJ, McCall JM, Ayer DE, Van Doornik FJ, Palmer JR, et al. Novel 21-aminosteroids that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma. Journal of Medicinal Chemistry 33: 1145–1151, 1990
Jadot G, Michelson AM, Puget K, Baret A. Antiinflammatory activity of Superoxide dismutases: inhibition of carrageenan-induced edema in rats. Free Radical Research Communications 1: 395–403, 1986
Jain SK, Williams DM. Reduced levels of plasma ascorbic acid (vitamin C) in sickle cell disease patients: its possible role in the oxidant damage to sickle cells in vivo. Clinica Chimica Acta 149: 257–261, 1985
Jandak J, Steiner M, Richardson PD. a-Tocopherol, an effective inhibitor of platelet adhesion. Blood 73: 141–149, 1989
Janero DR, Burghardt B, Lopez R. Protection of cardiac membrane phospholipid against oxidative injury by calcium antagonists. Biochemical Pharmacology 37: 4197–4203, 1988
Jones MM. Newer trends in therapeutic chelating agents. Trends in Pharmacological Sciences 3: 335–337, 1982
Jones MM. New developments in therapeutic chelating agents as antidotes for metal poisoning. Critical Reviews in Toxicology 21: 209–233, 1991
Jones MH, Pratt TH. Therapeutic chelating agents. Journal of Chemical Education 53: 342–347, 1976
Kaminski PM, Proctor KG. Actions of adenosine on nitroblue tetrazplium deposition and surface pH during intestinal reperfusion injury. Circulation Research 66: 1713–1719, 1990
Kanner J, Harel S. Initiation of membranal lipid peroxidation by activated metmyoglobin and methaemoglobin. Archives of Biochemistry and Biophysics 237: 314–321, 1985
Kanofsky JR. Singlet oxygen production by biological systems. Chemico-Biological Interactions 70: 1–28, 1989
Kappus H. A survey of chemicals inducing lipid peroxidation in biological systems. Chemistry and Physics of Lipids 45: 105–115, 1987
Kehrer JP, Concepts related to the study of reactive oxygen and cardiac reperfusion injury. Free Radical Research Communications 5: 305–314, 1989
Kontoghiorghes GJ. The study of iron mobilisation from transferrin using α-ketohydroxy heteroaromatic chelators. Biochimica et Biophysica Acta 869: 141–146, 1986a
Kontoghiorghes GJ. Iron mobilisation from lactoferrin by chelators at physiological pH. Biochimica et Biophysica Acta 882: 267–270, 1986b
Kontoghiorghes GJ, Jackson MJ, Lunec J. In vitro screening of iron chelators using models of free radical damage. Free Radical Research Communications 2: 115–124, 1986
Krinsky NI. Antioxidant functions of carotenoids. Free Radical Biology and Medicine 7: 617–635. 1989
Laguna JC, Nagi MN, Cook L, Cinti DL. Action of Ebselen on rat hepatic microsomal enzyme-catalyzed fatty acid chain elongation, desaturation and drug biotransformation. Archives of Biochemistry and Biophysics 269: 272–283, 1989
Larson RA. The antioxidants of higher plants. Phytochemistry 27: 969–978, 1988
Lasley RD, Ely SW, Berne RM, Mentzer RM Jr. Allopurinol enhanced adenine nucleotide repletion after myocardial ischemia in the isolated rat heart. Journal of Clinical Investigation 81: 16–20, 1988
Laughton MJ, Halliwell B, Evans PJ, Hoult JRS. Antioxidant and pro-oxidant actions of the plant phenolics quercetin, gossypol and myricetin. Biochemical Pharmacology 38: 2859–2865, 1989
Leurs H, Timmerman H, Bast A. Inhibition of Superoxide anion radical production by Ebselen (PZ51) and its sulfur analogue (PZ25) in guinea pig alveolar macrophages. Biochemistry International 18: 295–299, 1989
Levander OA. A global view of human selenium nutrition. Annual Review of Nutrition 7: 227–250, 1987
Levine M. New concepts in the biology and biochemistry of ascorbic acid. New England Journal of Medicine 314: 892–902, 1986
Lewis DAL. Anti-inflammatory drugs from plant and marine sources. Agents and Actions 27 (Suppl.): 1–373, 1989
Lunec J, Blake DR. The determination of dehydroascorbic acid and ascorbic acid in the serum and synovial fluid of patients with rheumatoid arthritis. Free Radical Research Communications 1: 31–39, 1985
Maly FE. The B lymphocyte: a newly recognized source of reactive mygen species with immunoregulatory potential. Free Radical Research Communications 8: 143–148, 1990
Marklund SL. Expression of extracellular Superoxide dismutase by human cell lines. Biochemical Journal 266: 213–219, 1990
Marietta MA. Nitric oxide: biosynthesis and biological significance. Trends in Biochemical Sciences 14: 488–492, 1989
Mathews-Roth MM. Photoprotection by carotenoids. Federation Proceedings 46: 1890–1893, 1987
McCarthy JT, Milliner DS, Johnson WJ. Clinical experience with desferrioxamine in dialysis patients with aluminium toxicity. Quarterly Journal of Medicine 74: 257–276, 1990
McCay PB. Vitamin E: interactions with free radicals and ascorbate. Annual Review of Nutrition 5: 323–340, 1985
McCord JM. Oxygen-derived free radicals in post ischemic tissue injury. New England Journal of Medicine 312: 159–163, 1985
McLachlan DRC, Dalton HJ, Kruch TPA, Bell MY, Smith WL, et al. Intramuscular desferrioxamine in patients with Alzheimer’s disease. Lancet 337: 1304–1308, 1991
McLaren GD, Muir WA, Kellermeyer RW. Iron overload disorders: natural history, pathogenesis, diagnosis and therapy. CRC Critical Reviews in Clinical Laboratory Science 19: 205–266, 1983
Meier B, Radeke HH, Selle S, Raspe HH, Sies H, et al. Human fibroblasts release reactive oxygen species in response to treatment with synovial fluids from patients suffering from arthritis. Free Radical Research Communications 8: 149–160, 1990
Meister A. Glutathione metabolism and its selective modification. Journal of Biological Chemistry 263: 17205–17208, 1988
Menasche P, Grousset C, Gauduel Y, Piwnica A. A comparative study of free radical scavengers in cardioplegic solutions. Journal of Thoracic and Cardiovascular Surgery 92: 264–271, 1986
Menasche P, Pasquier C, Belluci S, Lorente P, Jaillon P, et al. Deferoxamine reduces neutrophil-mediated free radical production during cardiopulmonary bypass in man. Journal of Thoracic and Cardiovascular Surgery 96: 582–589, 1990
Merry P, Winyard PG, Morris CJ, Grootveld M, Blake DR. Oxygen free radicals, inflammation and synovitis: the current status. Annals of the Rheumatic Diseases 48: 864–870, 1989
Miners JO, Drew R, Birkett DJ. Mechanism of action of paracetamol protective agents in mice in vivo Biochemical Pharmacology 33: 2995–3000, 1984
Minotti G, Aust SD. The role of iron in the initiation of lipid peroxidation. Chemistry and Physics of Lipids 44; 191–208, 1987
Mitchell JB, Samuni A, Krishna MC, de Graff WG, Ahm MS, et al. Biologically active metal-independent Superoxide dismutase mimics. Biochemistry 29: 2802–2807, 1990
Mitchinson MJ, Ball RY. Macrophages and atherogenesis. Lancet 2: 146–148, 1987
Modell B, Letsky EA, Flynn DM, Peto R, Weatherall DJ. Survival and desferrioxamine in thalassaemia major. British Medical Journal 284: 1081–1084, 1982
Moldeus P, Cotgreave IA, Berggren M. Lung protection by a thiolcontaining antioxidant: N-acetylcysteine. Respiration 50 (Suppl. 1): 31–42, 1986
Moroney MA, Alcaraz MJ, Forder RA, Carey F, Hoult JRS. Selectivity of neutrophil 5-lipoxygenase and cyclooxygenase inhibition by an anti-inflammatory flavonoid glycoside and related aglycone flavonoids. Journal of Pharmacy and Pharmacology 40: 787–792, 1988
Mukai K, Okabe K, Hosose H. Synthesis and stopped-flow investigation of antioxidant activity of tocopherols. Finding of new tocopherol derivatives having the highest antioxidant activity among phenolic antioxidants. Journal of Organic Chemistry 54: 557–560, 1989
Murrell GAC, Francis M JO, Bromley L. Free radicals and Dupuytren’s contracture. British Medical Journal 295: 1373–1375, 1987
Murrell GAC, Francis MJO, Bromley L. Modulation of fibroblast proliferation by oxygen free radicals. Biochemical Journal 265: 659–665, 1990
Myers PR, Minor Jr RL, Guerra Jr R, Bates JN, Harrison DG. Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble 5-nitrosocysteine than nitric oxide. Nature 345: 161–163, 1990
Nagano T, Hirano T, Hirobe M. Superoxide dismutase mimics based on iron in vivo Journal of Biological Chemistry 264: 9243–9249, 1989
Nathan DG, Piomelli S. Introduction: oral iron chelators. Seminars in Hematology 27: 83–85, 1990
Nienhuis AW. Vitamin C and iron. New England Journal of Medicine 304: 170–171, 1981
Nishino T, Tsushima K. Interaction of milk xanthine oxidase with folic acid. Journal of Biological Chemistry 261: 11242–11246, 1986
Okamoto H. Molecular basis of experimental diabetes: degeneration, oncogenesis and regeneration of pancreatic β-cells of islets of Langerhans. Bioessays 2: 15–21, 1986
Orrenius S, McConkey DJ, Bellomo G, Nicotera P. Role of Ca2+in toxic cell killing. Trends in Pharmacological Sciences 10: 281–285, 1989
Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. New England Journal of Medicine 321: 1364–1371, 1989
Parks DA. Oxygen radicals: mediators of gastrointestinal patho-physiology. Gut 30: 293–298, 1989
Parnham MJ, Leyck S, Graf E, Dowling EJ, Blake DR. The pharmacology of ebselen. Agents and Actions 32: 4–9, 1991
Parthasarathy S, Young SG, Witztum JL, Pittman RC, Steinberg D. Probucol inhibits oxidative modification of low density lipoprotein. Journal of Clinical Investigation 77: 641–644, 1986
Patel BS, Jeroudi MO, O’Neill PG, Roberts R, Bolli R. Effect of human recombinant Superoxide dismutase on canine myocardial infarction. American Journal of Physiology 258: H369–H380, 1990
Perry MA, Wadhwa SS. Gradual reintroduction of oxygen reduces reperfusion injury in cat stomach. American Journal of Physiology 254: G366–G372, 1988
Petch MC. Dangers of thrombolysis. British Medical Journal 300: 483, 1990
Peterhans E, Jungi TW, Stocker R. Autotoxicity and reactive oxygen in viral disease. In Cerutti PA et al. (Eds) Oxy-radicals in molecular biology and pathology, pp. 543–562, AR Liss Inc., New York, 1988
Pitarys CJ, Virmani R, Vildibill HD, Jackson EK, Forman MB. Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period. Circulation 83: 237–247, 1991
Pollack S, Rossan RN, Davidson DE, Escajadillo A. Desferriox-amine suppresses Plasmodium falciparumin Astus monkeys. Proceedings of the Society for Experimental Biology and Medicine 184: 162–164, 1987
Porta P, Aebi S, Summer K, Lauterburg BH. L-2-oxothiazolidine-4-carboxylic acid, a cysteine prodrug: pharmacokinetics and effects on thiols in plasma and lymphocytes in human. Journal of Pharmacology and Experimental Therapeutics 257: 331–334, 1991
Porter JB, Hoyes KP, Abeysinghe R, Huehns ER, Hider RC. Animal toxicology of iron chelator LI. Lancet ii: 156, 1989b
Porter JB, Jaswon MS, Huehns ER, East CA, Hazell JWP. Desferrioxamine ototoxicity: evaluation of risk factors in thalas-saemic patients and guidelines for safe dosage. British Journal of Haematology 73: 403–409, 1989a
Porter JB, Morgan J, Hoyes EP, Burke LC, Huehns ER, Hider RC. Relative oral efficacy and acute toxicity of hydroxypyrid-4-one iron chelators in mice. Blood 76: 2389–2396, 1990
Powis G. Free radical formation by antitumpr quinones. Free Radical Biology and Medicine 6: 63–101, 1989
Puppo A, Halliwell B. Formation of hydroxyl radicals from hydrogen peroxide in the presence of iron: is haemoglobin a biological Fenton reagent? Biochemical Journal 249: 185–190, 1988a
Puppo A, Halliwell B. Formation of hydroxyl radical in biological systems. Does myoglobin stimulate hydroxyl radical formation from hydrogen peroxide? Free Radical Research Communications 4: 415–422, 1988b
Puppo A, Cecchini R, Aruoma OI, Bolli R, Halliwell B. Scavenging of hypochlorous acid and of myoglobin-derived oxidants by the cardioprotective agent mercaptopropionylglycine. Free Radical Research Communications 10: 371–381, 1990
Reddanna P, Rao MK, Reddy CC. Inhibition of 5-lipoxygenase by vitamin E. FEBS Letters 193: 39–43, 1985
Reiter S, Simmonds HA, Webster DR, Watson AR; On the metabolism of allopurinol]. Biochemical Pharmacology 32: 2167–2174, 1
Rinaldo JE, Gorry M. Protection by deferoxamine from endo-thelial injury: a possible link with inhibition of intracellular xanthine oxidase. American Journal of Respiratory Cell and Molecular Biology 3: 525–533, 1990
Ross D. Glutathione, free radicals and chemotherapeutic agents. Pharmacology and Therapeutics 37: 231 -249, 1988
Roubal WT, Tappel AL. Damage to proteins, enzymes and amino acids by peroxidizing lipids. Archives of Biochemistry and Biophysics 113: 5–8, 1966
Rowley DA, Halliwell B. Superoxide-dependent formation of hydroxyl radicals in the presence of thiol compounds. FEBS Letters 138: 33–36, 1982
Saez G, Thornalley PJ, Hill HAO, Hems R, Bannister JV. The production of free radicals during the autoxidation of cysteine and their effect on isolated rat hepatocytes. Biochimica et Biophysica Acta 719: 24–31, 1982
Salim AS. Oxygen-derived free radicals and the prevention of duodenal ulcer relapse: a new approach. American Journal of Medical Sciences 300: 1–6, 1990
Salvemini D, Botting R. The effect of free radical scavengers on platelet adhesion and aggregation. Drug News and Perspectives 3: 202–212, 1990
Sanan S, Sharma G, Malhotra R, Sanan DP, Jain P, et al. Protection by desferrioxamine against histopathological changes of the liver in the post-oligaemic phase of clinical haemorrhagic shock in dogs: correlation with improved survival rate and recovery. Free Radical Research Communications 6: 29–38, 1989
Sanfey H, Bulkley GB, Cameron JL. The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis. Annals of Surgery 200: 405–413, 1984
Saran M, Michel C, Bors W. Reaction of NO with Superoxide. Free Radical Research Communications 10: 221–226, 1990
Schalkwijk J, van den Berg WB, van de Putte LBA, Joosten LAB, van den Bersselaar L. Cationization of catalase, peroxidase and Superoxide dismutase. Journal of Clinical Investigation 76: 198–205, 1985
Schneeburger H, Illner WD, Abendroth D, Bulkley G, Rutili F, et al. First clinical experiences with Superoxide dismutase in kidney transplantation —results of a double-blind randomized study. Transplantation Proceedings 21: 1245–1246, 1989
Schneider J. Prophylactic and curative effects of recombinant human Superoxide dismutase in lethal rat endotoxemia. Arzneimittel Forschung Drug Research 38: 1381–1386, 1988
Schöneich C, Asmus KD, Dillinger U, von Bruchhausen F. Thiyl radical attack on polyunsaturated fatty acids: a possible route to lipid peroxidationj Biochemical and Biophysical Research Communications 161: 113-120, 1989
Schraufstatter IU, Hysloi PA, Jackson J, Cochrane CG. Oxidant injury of cells. International Journal of Tissue Reactions IX: 317–324, 1987
Sevanian A, Peterson AR. The cytotoxic and mutagenic properties of cholesterol oxidation products. Food Chemistry and Toxicology 24: 1103–1110, 1986
Sevilla MD, Yan M, Becker D, Gillich S. ESR investigations of the reactions of radiation-produced thiyl and DNA peroxyl radicals: formation ofjsulfbxyl radicals. Free Radical Research Communications 6: 21–24, 1989
Shamberger RJ. Genetic toxicology of ascorbic acid. Mutation Research 133; 135–159, 1984
Shapiro A, Nathan HC, Hutner SH, Garofalo J, McLaughlin SD, et al. In vivo and in vitro activity by diverse chelators against Trypanosoma brucei brucei Journal of Protozoology 29: 85–90, 1982
Sik RH, Paschall CS, Chignell CF. The phototoxic effect of benoxaprofen and its analogs on human erythrocytes and rat peritoneal mast cells. Photochemistry and Photobiology 38: 411–415, 1983
Simons JM, Hart BA, Ching TRIV, Van Dijk HV, Labadie RP. Metabolic activation of natural phenols into selective oxidative burst agonists by activated human neutrophils. Free Radical Biology and Medicine 8: 251–258, 1990
Simpson PJ, Lucchesi BR. Free radicals and myocardial ischaemia and reperfusion injury. Journal of Laboratory and Clinical Medicine 110: 13–30, 1987
Sinha S, Davies J, Toner N, Bogle S, Chiswick M. Vitamin E supplementation reduces frequency of periventricular haemorrhage in very preterm babies. Lancet 1: 466–470, 1987
Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. New England Journal of Medicine 319: 1557–1562, 1988
Smith LL. Cholesterol autoxidation 1981-1986. Chemistry and Physics of Lipids 44; 87–100, 1987
Sorenson JRJ. Bis(3,5-diisopropylsalicylato)copper(II), a potent radioprotectant with Superoxide dismutase mimetic activity. Journal of Medicinal Chemistry 27: 1747–1749, 1984
Spector T. Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of Superoxide radical. Biochemical Pharmacology 37: 349–352, 1988
Spector T, Hall WW, Porter DJT, Lambe CU, Nelson DJ, et al. Inhibition of xanthine oxidase by 4-hydroxy-6-mercaptopyrazolo[3,4-d]pyrimidine. Biochemical Pharmacology 38: 4315–4320, 1989
Speyer JL, Green MD, Kramer E, Rey M, Sanger J, et al. Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer. New England Journal of Medicine 319: 745–752, 1988
Stähelin HB, Gey L-F, Eichholzer M, Lüdin E. β-carotene and cancer prevention: the Basel study. American Journal of Clinical Nutrition 53: 2655–2695, 1991
Starke PE, Färber JL. Ferric iron and Superoxide ions are required for the killing of cultured hepatocytes by hydrogen peroxide. Journal of Biological Chemistry 260: 10099–10104, 1985
Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. New England Journal of Medicine 320: 915–924, 1989
Steinke DE, Weir BKA, Findlay JM, Tanabe T, Grace M, et al. A trial of the 21-aminosteroid U74006F in a primate model of chronic cerebral vasospasm. Neurosurgery 24: 179–186, 1989
Steinkuhler C, Mavelli I, Rossi L, Pedersen JZ, Melino G, et al. Cytotoxicity of a low molecular weight CU2Zn2Superoxide dismutase active center analog in human erythroleukemia cells. Biochemical Pharmacology 39: 1473–1479, 1990
Stern LZ, Ringel SP, Ziter FA, Menander-Huber KB, Ionasescu V, et al. Drug trial of Superoxide dismutase in Duchenne’s muscular dystrophy. Archives of Neurology 39: 342–344, 1982
Stocker R. Induction of haem oxygenase as a defence against oxidative stress. Free Radical Research Communications 9: 101–112, 1990
Stowell KM, Rado TA, Funk WD, Tweedie JW. Expression of cloned human lactoferrin in baby-hamster kidney cells. Biochemical Journal 276: 349–355, 1991
Suzuki M, Inauen W, Kvietys PR, Grisham MB, Meininger C, et al. Superoxide mediates reperfusion-induced leukocyte-endothelial cell interactions. American Journal of Physiology 257: H1740–H1745, 1989
Svardal AM, Mansoor MA, Ucland PM. Determination of reduced, oxidized, and protein-bound glutathione in human plasma with precolumn derivatization with monobromobimane and liquid chromatography. Analytical Biochemistry 184: 338–346, 1990
Swingle KF, Bell RL, Moore GGI. Anti-inflammatory activity of antioxidants. In Rainsford KD (Ed.) Anti-inflammatory and anti-rheumatic drugs, Vol. III, CRC Press, Boca Raton, 1987
Tabor E, Epstein JS, Hewlett JK, Lee SF. Inhibition by desfer-rioxamine of in-vitro replication of HIV-I. Lancet 337: 795, 1991
Tannenbaum SR, Wishnock JS, Leaf CD. Inhibition of nitrosamine formation by ascorbic acid. American Journal of Clinical Nutrition 53: 247S–250S, 1991
Thomas MJ, Bielski BHJ. Oxidation and reaction of Trolox C, a tocopherol analogue, in aqueous solution: a pulse-radiolysis study. Journal of the American Chemical Society 111: 3315–3319, 1989
Thornalley PK. Esterification of reduced glutathione. Biochemical Journal 275: 535–537, 1991
Thumwood CM, Hunt NH, Cowden WB, Clark IA. Antioxidants can prevent cerebral malaria in Plasmodium berghei-infected mice. British Journal of Experimental Pathology 70: 293–303, 1989
Tibell L, Hjalmarsson K, Edlund T, Skogman G, Engstrom A, et al. Expression of human extracellular Superoxide dismutase in Chinese hamster ovary cells and characterization of the product. Proceedings of the National Academy of Sciences of the USA 84: 6634–6638, 1987
Tryka AF. ICRF-187 and polyhydroxyphenyl derivatives fail to protect against bleomycin induced lung injury. Toxicology 59: 127–138, 1989
Tsao CS, Salimi SL. Evidence of rebound effect with ascorbic acid. Medical Hypotheses 13: 303–310, 1984
Tsao PS, Lefer AM. Time course and mechanism of endothelial dysfunction in isolated ischemic-and hypoxic-perfused rat hearts. American Journal of Physiology 259: H1660–H1666, 1990
Ucland PM, Refsum H. Plasma homocysteine, a risk factor for vascular disease: plasma levels in health, disease and drug therapy. Journal of Laboratory and Clinical Medicine 114: 473–501, 1989
Vaille A, Jadot G, Elizagaray A. Anti-inflammatory activity of various Superoxide dismutases on polyarthritis in the Lewis rat. Biochemical Pharmacology 39: 247–255, 1990
Van der Wal NAA, Van Oirschot JFLM, Van Dijk A, Verhoef J, Sweder Van Asbeck B. Mechanism of protection of alveolar type II cells against paraquat-induced cytotoxicity by deferoxamine. Biochemical Pharmacology 39: 1665–1671, 1990
Villar A, Gasco MA, Alcaraz MJ. Anti-inflammatory and anti-ulcer properties of hypolactin-8-glucoside, a novel plant flavonoid. Journal of Pharmacy and Pharmacology 36: 820–823, 1984
Vohra K, Rosenfeld W, Singh I, Anderson V. Ischemic injury to newborn rabbit ileum: protective role of human Superoxide dismutase. Journal of Pediatric Surgery 24: 893–898, 1989
Von Sonntag C. The chemical basis of radiation biology, Taylor and Francis, London, 1987
Wajner M, Harkness RA. Distribution of xanthine dehydrogenase and oxidase activities in human and rabbit tissues. Biochimica et Biophysica Acta 991: 79–84, 1989
Wang Q, Giri SN, Hyde DM, Nakashima JM, Javadi I. Niacin attenuates bleomycin-induced lung fibrosis in the hamster. Journal of Biochemical Toxicology 5: 13–22, 1990
Ward HE, Hicks M, Nicholson A, Berend N. Deferoxamine infusion does not inhibit bleomycin-induced lung damage in the rat. American Review of Respiratory Disease 137: 1356–1359, 1988
Ward PA, Till GO, Kunkel R, Beauchamp C. Evidence of role of hydroxyl radical in complement and neutrophil-mediated tissue injury. Journal of Clinical Investigation 72: 789–801, 1983
Warso MA, Lands WEM. Lipid peroxidation in relation to prostacyclin and thromboxane physiology and pathophysiology. British Medical Bulletin 39: 277–280, 1983
Wasil M, Halliwell B, Hutchison DCS, Baum H. The antioxidant action of extracellular fluids. Biochemical Journal 243: 219–223, 1987
Wefers H. Singlet oxygen in biological systems. Bioelectrochemistry and Bioenergetics 18: 91–104, 1987
Weiss APC, Carey LA, Randolph MA, Moore JR, Weiland AJ. Oxygen radical scavengers improve vascular potency and bone-muscle cell survival in an ischemic extremity replant model. Plastic and Reconstructive Surgery 84: 117–123, 1989
Weiss SJ. Tissue destruction by neutrophils. New England Journal of Medicine 320: 365–376, 1989
Weitberg AB. Effect of nicotinic acid supplementation in vivo on oxygen radical-induced genetic damage in human lymphocytes. Mutation Research 216: 197–201, 1989
Werns SW, Lucchesi BR. Free radicals and ischemic tissue injury. Trends in Pharmacological Sciences 11: 161–166, 1990
Weser U, Sellinger KH, Lengfelder E, Werner W, Strahle J. Structure of Cu2(indomethacin)4and the reaction with Superoxide in aprotic systems. Biochimica et Biophysica Acta 631: 232–245, 1980
White GJ. Inhibition of oxidation enzymes by anti-allergy drugs. Agents and Actions 11: 503–509, 1981
Wolfe LC. Desferrithiocin. Seminars in Hematology 27: 117–120, 1990
Wolff SP, Dean RT. Glucose autoxidation and protein modification. Biochemical Journal 245: 243–250, 1987
Yokode M, Kita T, Kikawa Y, Ogorochi T, Narumiya S, et al. Stimulated arachidonate metabolism during foam cell transformation of mouse peritoneal macrophages with oxidized low density lipoprotein. Journal of Clinical Investigation 81; 720–729, 1988
Yoon JO, Im MJ, Manson PN, Bulkley GB, Hoopes JE. The role of metal ions in ischemia/reperfusion injury in skin flaps. Journal of Surgical Research 46: 163–165, 1989
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Halliwell, B. Drug Antioxidant Effects. Drugs 42, 569–605 (1991). https://doi.org/10.2165/00003495-199142040-00003
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199142040-00003