Abstract
The physiological role of heme containing peroxidases in circulating or tissue infiltrating white cells, polymorphonuclear leukocytes, monocytes and eosinophils is to enable these cells to carry out their function of killing invading bacteria, viruses, parasites, protozoa, etc. or tumor cells. Another role is to inactivate regulators released into the blood stream such as estradiol, leukotrienes and chemotactic factors. The peroxidases in these cells are soluble but are located in granules or lysosomes. They are released into phagocytic vacuoles and/or from the cell when the cells are activated by invading microorganisms. Lactoperoxidase secreted into body fluids from the mammary gland, Zymbal gland, salivary gland, lacrimal gland and Harderian glands, etc may also play a role in killing invading organisms in body fluids. Peroxidases located in the rough endoplasmic reticular membrane and nuclear envelope of other cells are not released from the cell and are probably more concerned with the synthesis of regulators (eg. thyroxine by thyroid peroxidase, prostaglandin by prostaglandin synthetase) or the inactivation of regulators (eg. oestradiol by uterine peroxidase). The peroxidase of resident peritoneal macrophages or Kupffer cells of the liver are also located in the endoplasmic reticulum but are not discharged to phagocytic vacuoles so that their function may not be antimicrobial. Intestinal peroxidase and another uterine peroxidase have been attributed to infiltrated eosinophils whereas spleen peroxidase has been attributed to infiltrated monocytes (Banerjee, 1988). Peroxidases are therefore ubiquitous in tissues either as a result of endogenous activity or as a result of infiltrated white blood cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Banerjee, R.K. (1988). Membrane peroxidases. Molec. Cell. Biochem. 83, 105–128.
Boyd, J.A. and Eling, T.E. (1981). Prostaglandin endoperoxide synthetase dependent cooxidation of acetaminophen to intermediates which covalently bind to rabbit renal medullary microsomes. J. Pharmacol. Exp. Ther 219, 659–664.
Boyd, J.A. and Eling, T.E. (1985). Metabolism of aromatic amines by prostaglandin H sunthase. Environ. Health Perspect. 64, 45–51.
Corbett, M.D. and Corbett, B.R. (1988). Metabolic activation and nucleic acid binding of acetaminophen and related amines during the respiratory burst of human gramlocytes. Chem. Res. Toxicol. 2, 260–267.
Dahlin, D.C., Miwa, G.T., Lu, A.Y.H. and Nelson, S.D. (1984). N-acetyl-p-benzoquinoneimine: a cytochrome P-450 mediated oxidation product of acetaminophen. Proc. Natl. Acad. Sci. 81, 1327–1331.
Fahimi, H.D., Gray, B.A. and Herzog, V.K. (1976). Cytochemical localization of catalase and peroxidase in sinusoidal cells of rat liver. Laboratory Investigation 34, 192–201.
Fernando, C.R., Calder, I.C. and Ham, K.N. (1980). Studies on the mechanism of toxicity of acetaminophen. Synthesis and reactions of N-acety1–2,6-dimethyl-p-benzoquinone imines. J. Medic. Chem. 23, 1153–1158.
Ferluga, J. and Allison, A. (1978). Role of mononuclear infiltrating cells in pathogenetics of hepatitis. Lancet 2, 610–611.
Foote, C.S., Goyne, T.E. and Lehrer, R.I. (1983). Assessment of chlorination by human neutrophils. Nature 301, 715–716.
Grisham, M.B., Jefferson, M.M., Melton, D.F. and Thomas, E.L. (1984). Chlorination of endogenous amines by isolated neutrophils. J. Biol. Chem. 259, 10404–10412.
Guarna, A., Corte, L.D., Giovannini, M.G., De Sarlo, F. and Sgaragli, G. (1983). A dimer metabolite of 2t-buty1–4-methoxyphenol in the rat. Drug Metab. Dispos. 11, 581–584.
Hanel, A.M. and Lands, W.E.M. (1982). Modification of anti-inflammatory drug effectiveness by ambient lipid peroxides. Biochem. Pharmacol. 31, 3307–3311.
Harvison, P.J., Guengerich, F.P., Rashed, M.S. and Nelson, S.D. (1988). Cytochrome P-450 isozyme selectivity in the oxidation of acetaminophen. Chem. Res.Toxicol. 1, 47–52.
Jaeschke, H. and Mitchell, J.R. (1988). Acetaminophen toxicity. New Engl. J. Med. 319, 1601–1602.
Josephy, D. (1988). Activating aromatic amines by prostaglandin synthetose. Free Rad. Biol. Med. 6, 533–542.
Krauss, R.S., Angerman-Stewart, J., Eling, T.E., Dooley, K.L. and Kadlubar, F.F. (1989). The formation of 2-aminofluorene-DNA adducts in vivo: evidence for peroxidase-mediated activation. J. Biochem. Toxicol. 4, 111–117.
Laskin, D.L., Robertson, F.M., Pilaro, A.M. and Laskin, J.D. (1988). Activation of liver macrophages following phenobarbital treatment of rats. Hepatology 8, 1051–1055.
Laskin, D.L., Pilaro, A.M. and Sungchul, J. (1986). Potential role of activated macrophages in acetaminophen hepatotoxicity. Toxicol. Appl. Pharmacol. 86, 216–226
Lauterburg, B.H. and Velez, M.E. (1988). Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity. Gut. 29, 1153–1157.
Licht, H., Seeff, I.B. and Zimmermann, H.J. (1980). Apparent potentiation of acetaminophen hepatotoxicity by alcohol. Ann. Intern. Med. 92, 511.
Mason, R.P. and Fischer, V. (1986). Free radicals of acetaminophen: their subsequent reactions and toxicological significance. Federation Proc. 45, 2493–2499.
McClain, C.J., Kromhout, J.P., Peterson, F.J. and Holtzman, J.L. (1980). Potentiation of paracetamol hepatotoxicity by alcohol. JAMA 244, 251–253.
MacSween, R.N.M. (1981). Alcoholic liver disease: morphological manifestations: review by an international group. Lancet 1, 707.
Marnett, L.J. and Eling, T.E. (1983). Cooxidation during prostaglandin biosynthesis: a pathway for the metabolic activation of xenobiotics. Rev. Biochem. Toxicol. 5, 135–172.
Mayeno, A.N., Curran, A.J., Roberts, R.L. and Foote, C.S. (1989). Eosinophils preferentially use bromide to generate halogenating agents. J. Biol. Chem. 264, 5660.
Meunier, B. (1987). Horseradish peroxidase: a useful tool for modeling the extra-hepatic biooxidation of oxogens. Biochimie 69, 3–9.
Mohandas, J., Duggin, G.G., Horvath, J.S. and Tiller, D.J. (1981). Metabolic oxidation of acetaminophen mediated by cytochrome P-450 mixed function oxidase and prostaglandin endoperoxide synthetase in rabbit kidney. Toxicol. Appl. Pharmacol. 61, 252–259.
Moldeus, P. and Rahimtula, A. (1980). Metabolism of paracetamol to a glutathione conjugate catalysed by prostaglandin synthetase. Biochem. Biophys. Res. Comm. 96, 469–475.
Moldeus, P., Hogberg, J. and Orrenius, S. (1978). Isolation and use of liver cells. Methods Enzymol. 52, 60–66.
Moldeus, P., Andersson, B., Rahimtula, A. and Berggren, M. (1982). Prostaglandin synthetase catalysed activation of paracetamol. Biochem. Pharmacol. 31, 1363–1370.
O’Brien, P.J. (1984). Multiple mechanisms for the metabolic activation of carcinogenic arylamines. Free Radicals in Biology VI (Pryor, W.A., ed), pp. 289–322, Academic Press.
O’Brien, P.J. (1985). Free-Radical Mediated DNA binding. Env. Health Perspect. 64, 219–232.
O’Brien, P.J. (1988a). Radical formation during the peroxidase catalyzed metabolism of carcinogens and xenobiotics. Free Radicals Biol. Med. 4, 169–183.
O’Brien, P.J. (1988b). Oxidants formed by the respiratory burst: their physiological role and their involvement in the oxidative metabolism and activation of drugs. The Respiratory Burst and Its Physiological Significance (Sbarra, A.J., and Strauss, R.R., eds) pp. 203–232, Plenum Press.
O’Brien, P.J. (1990a). Activation of xenobiotics by hypohalites or peroxidases, H2O2 and halide in Biological Oxidation Systems. Ed. Reddy, C.C., Hamilton, G.A. and Madyastha, K.M. Academic Press, N.Y.
O’Brien, P.J., Gregory, B., Fanney, R., Davison, W., Rahintula, A.D. and Tsuruta, Y. (1985). Microsomes and Drug Oxidations (Boobis, A.R., Caldwell, J., de Matteis, F., and Elcombe, C.R., eds) pp. 100–112, Taylor and Francis Ltd., London.
O’Brien, P.J., Jatoe, S., McGirr, L. G., Khan, S. (1990b). Molecular activtion mechanisms involved in arylamine cytotoxicity: ’ peroxidase products in “N-oxidation of Drugs”, Biochemistry, Pharmacology and Toxicology, Ed. Hlavica, P., Damani, L.A., and Gorrod, J.W., Chapman and Hall (in press).
Pilaro, A.M. and Laskin, D.L. (1986). Accumulation of activated mononuclear phagocytes in the liver following lipopolysaccharide treatment of rats. J. Leukocyte Biology 40, 29–41.
Porubek, D.J., Rundgren, M., Harrison, P.J., Nelson, S.D. and Moldeus, P. (1987). Investigation of mechanisms of acetaminophen toxicity in isolated rat hepatocytes with acetaminophen analogues. Molec. Pharmacol. 31, 647–653.
Potter, D.W. and Hinson, J.A. (1987a). Mechanisms of acetaminophen oxidation to N-acetyl-p-benzoquinoneimine by horseradish peroxidase and cytochrome P-450. J. Biol. Chem. 262, 966–973.
Potter, D.W. and Hinson, J.A. (1987b). The one and two-electron oxidation of acetaminophen catalysed by prostaglandin H synthase. J. Biol. Chem. 262, 974–980.
Prescott, L.G. (1983). Paracetamol Overdosage. Drugs 25, 290–314.
Ritter, C.L. and Malejka-Giganti, D. (1989). Oxidations of the carcinogen N-hydroxy-N-(2-fluorenyl) acetamide by enzymatically or chemically generated oxidants of chloride and bromide. Chem. Res. Toxicol. 2, 325–333.
Ross, D., Norbeck, K. and Moldeus, P. (1985). The generation and subsequent fate of glutathionyl radicals in biological systems. J. Biol. Chem. 260, 15028–15032.
Rice, R.G. and Gomez-Taylor, M. (1986). Occurrence of by-products of strong oxidants reacting with drinking water contaminants. Env. Health Perspectives 69, 31–44.
Sato, C., Matsuda, Y. and Lieber, C.S. (1981). Increased hepatotoxicity of acetaminophen after chronic ethanol consumption in the rat. Gastroenterology 80, 140–148.
Thomas, E.L., Grisham, M.B. and Jefferson, M.M. (1983). Myeloperoxidase dependent effect of amines on functions of isolated neutrophils. J. Clin. Invest. 72, 441–453.
Tsuruta, Y., Subrahmanyam, V.V., Marshall, W. and O’Brien, P.J. (1985). Peroxidase mediated irreversible binding of arylamine carcinogens to DNA intact polymorphonuclear leukocytes activated by a tumour promoter. Chem.-Biol. Interacn. 53, 25–35.
Uetrecht, J.P. (1988). Drug-induced agranulocytosis and other effects mediated by peroxidases during the respiratory burst. The Respiratory Burst and Its Physiological Significance (Sbarra, A.J., and Strauss, R.R., eds) pp. 233–244, Plenum Press.
Uetrecht, J.P. (1989). Idiosyncratic Drug Reactions: possible role of reactive metabolites generated by leukocytes. Pharmaceutical Research 6, 265–273.
Van Berkel, T.J. (1974). Difference spectra, catalase-and peroxidase activities of isolated parenchymal and non-parenchymal cells from rat liver. Biochem. biophys. Res. Comm. 61, 204–209.
Weiss, S.J. (1986). Chlorinated oxidants generated by leukocytes. Adv. in Free Radical Biology and Medicine 2, 91–106.
Weiss, S.J., Test, S.T., Eekmann, C.M., Roos, D. and Regiane, D. (1986). Brominating oxidants generated by human eosinophils. Science 234, 200–203.
Yamazoe, Y., Miller, D.W., Weiss, C.C., Dooley, K.L., Zenser, T.V., Beland, F.A. and Kadlubar, F.F. (1985). DNA adducts formed by ring-oxidation of the carcinogen 2-naphthylamine with prostaglandin H synthase in vitro and in dog urothelium in vivo. Carcinogenesis, 6, 1379–1387.
Yamazoe, Y., Zenser, T.V., Miller, D.W. and Kadlubar, F.F. (1989). The benzidine: DNA adduct formed by peroxidase and H202. Carcinogenesis 9, 1635–1641.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Plenum Press, New York
About this chapter
Cite this chapter
O’Brien, P.J., Khan, S., Jatoe, S.D. (1991). Formation of Biological Reactive Intermediates by Peroxidases: Halide Mediated Acetaminophen Oxidation and Cytotoxicity. In: Witmer, C.M., Snyder, R.R., Jollow, D.J., Kalf, G.F., Kocsis, J.J., Sipes, I.G. (eds) Biological Reactive Intermediates IV. Advances in Experimental Medicine and Biology, vol 283. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5877-0_5
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5877-0_5
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5879-4
Online ISBN: 978-1-4684-5877-0
eBook Packages: Springer Book Archive