Summary
Previous studies have shown that high doses of TCDD induce hepatic lipid peroxidation and inhibit selenium dependent glutathione peroxidase (GSH-Px) activity. The dose dependent effects of TCDD on hepatic lipid peroxidation (malondialdehyde content) and GSH-Px activity were determined. A dose as low as 1 μg/kg induced hepatic lipid peroxidation and inhibited GSH-Px. Based on the use of scavengers of reactive oxygen species, lipid peroxidation (malondialdehyde formation) by hepatic microsomes from both control and TCDD-treated rats appears to be due primarily to H2O2. The results indicate that superoxide, hydroxyl radical and singlet oxygen are also involved. The differences in the reactive oxygen species involved in microsomal lipid perexidation between control and TCDD treated animals appear to be quantitative rather than qualitative. A 5.9-fold greater rate of malondialdehyde (MDA) formation by microsomes from TCDD treated animals occurred as compared to controls, while livers of TCDD rats had an MDA content that was 5.0-fold greater than the controls. These differences may be due in part to an enhanced production of H2O2 as well as a decrease in the activity of selenium dependent glutathione peroxidase which metabolizes H2O2.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
J. S. Bus, and J. E. Gibson, Lipid peroxidation and its role in toxicology, Rev. Biochem. Toxicol. 1: 125 (1979).
A. L. Tappel, B. Fletcher, and D. W. Deamer, Effects of antioxidants and nutrients on lipid peroxidation fluorescent products and aging parameters in the mouse, J. Gerontol. 28: 415 (1973).
P. Hochstein, and L. Ernster, ADP—activated lipid peroxidation coupled to the TPNH oxidase system of microsomes, Biochem. Biophys. Res. Commun. 12: 388 (1963).
D. J. Kornbrust, and R. D. Mavis, Microsomal lipid peroxidation, Mol. Pharmacol. 17: 408 (1980).
E. D. Wills, Mechanism of lipid peroxide formation in animal tissues, Biochem. J. 99: 667 (1966).
T. J. Player, D. J. Mills, and A. A. Horton, Age—dependent chafiges in rat liver microsomal and mitochondrial NADPH—dependent lipid peroxidation, Biochem. Biophys. Res. Comm. 78: 1397 (1977).
V. A. Vlademirov, V. I. Olenev, T. B. Suslova, and Z. P. Cheremisina, Lipid peroxidation in mitochondrial membrane, Adv. Lipid Res. 17: 173 (1980).
T. C. Pederson, and S. D. Aust, NADPH—dependent lipid peroxidation catalyzed by purified NADPH cytochrome c reductase from rat liver microsomes, Biochem. Biophys. Res Commun. 48: 789 (1972).
R. J. Kociba, and B. A. Schwetz, Toxicity of 2,3,7,8—tetrachlorodibenzo—p—dioxin (TCDD), Drug. Met. Rev. 13: 387 (1982).
A. Poland, and J. C. Knutson, 2,3,7,8—Tetrachlorodibenzo—p—dioxin and related halogenated aromatic hydrocarbons: Examination of the mechanism of toxicity, Ann. Rev. Pharmacol. Toxicol. 22: 517 (1982).
S. J. Stohs, M. Q. Hassan, and W. J. Murray, Lipid peroxidation as a possible cause of TCDD toxicity, Biochem. Biophys. Res. Commun. 11: 854 (1983).
M. Q. Hassan, S. J. Stohs, and W. J. Murray, Comparative ability of TCDD to induce lipid peroxidation in rats, guinea pigs and Syrian golden hamsters, Bull. Environ. Contam. Toxicol. 31: 649 (1983).
R. A. Sunde, and W. G. Hoekstra, Structure, synthesis and function of glutathione peroxidase, Nutr. Rev. 38: 265 (1980).
A. W. Girotti, and J. P. Thomas, Superoxide and hydrogen peroxide-dependent lipid peroxidation in intact and Triton-dispersed erythrocyte membranes, Biochem. Biophys. Res. Comm. 118: 474 (1984).
O. H. Lowry, A. L. Rosebrough, A. L. Farr, and R. J. Randall, Protein measurement with the folin-phenol reagent, J. Biol. Chem. 193: 265 (1951).
P. R. Miles, J. R. Wright, L. Bowman, and H. D. Colby, Inhibition of hepatic microsomal lipid peroxidation by drug substrates without drug metabolism, Biochem. Pharmacol. 29: 565 (1980).
M. Uchiyama, and M. Mihara, Determination of malondialdehyde precursor in tissues by thiobarbituric acid test, Anal. Biochem. 86: 271 (1978).
J. R. Gillette, B. B. Brodie, and B. N. LaDu, The oxidation of drugs by liver microsomes: on the role of TPNH and oxygen, J Pharmacol. Exptl. Ther. 111: 532 (1957).
R. W. Estabrook, C. Martin-Wixtrom, Y. Saehi, R. Renneberg, A. Hildebrandt, and J. Werringloer, The peroxidatic function of liver microsomal cytochrome P-450: comparison of hydrogen peroxide and NADPII-catalyzed N-demethylation reactions, Xenobiotica 14: 87 (1984).
Y. Ohta, I. Ishiguro, J. Matto, and R. Shinohara, Effect of superoxide dismutase on hydroxylase activity and hydrogen peroxide formation in anthranilamide hydroxylation by a rat liver microsomal monooxygenase system, Biochem. lnt. 8: 617 (1984).
H. Kuthan and V. Ullrich, Oxidase and oxygenase function of the microsomal cytochrome P-450 monooxygenase system, Eur. J. Biochem 126: 583 (1982).
A. Bast, and G. R. M. M. Haenen, Cytochrome P-450 and glutathione: what is the significance of their interrelationship in lipid peroxidation?, Trends Biol. Sci. 9: 510 (1984).
R. Dixit, H., Mukhtar, and D. R. Bickers, Evidence that lipid peroxidation in microsomal membranes of epidermis is associated with generation of hydrogen peroxide and singlet oxygen, Biochem. Biophys. Res. Commun. 105: 546 (1982).
C. E. Thomas, L. A. Morehouse, and S.D. Aust, Ferritin and superoxide-dependent lipid peroxidation, J. Biol. Chem. 260: 3275 (1985).
G. H. Posner, J. R. Lever, K. Miura, C. Lisek, H. H. Seliger, and A. Thompson, A chemiluminescent probe specific for singlet oxygen, Biochem. Biophys. Res. Commun. 123: 869 (1984).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1986 Plenum Press, New York
About this chapter
Cite this chapter
Stohs, S.J., Al-Bayati, Z.F., Hassan, M.Q., Murray, W.J., Mohammadpour, H.A. (1986). Glutathione Peroxidase and Reactive Oxygen Species in TCDD-Induced Lipid Peroxidation. In: Kocsis, J.J., Jollow, D.J., Witmer, C.M., Nelson, J.O., Snyder, R. (eds) Biological Reactive Intermediates III. Advances in Experimental Medicine and Biology, vol 197. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5134-4_33
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5134-4_33
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5136-8
Online ISBN: 978-1-4684-5134-4
eBook Packages: Springer Book Archive