Abstract
During the last decades it has been recognized (1–3) that peroxidation of cellular membranes is an important event in the pathogenetic mechanisms of the liver injury induced by chemicals, such as CC14 or BrCCl3 , which give, upon metabolism, reactive free radicals. The latter ones alkylate cellular macromolecules but do not induce glutathione (GSH) depletion. It was subsequently shown (4–9) that lipid peroxidation is also strictly associated with the liver necrosis induced by chemi cals, such as bromobenzene and acetaminophen, which are converted to electrophilic intermediates giving extensive GSH conjugation and consequent GSH depletion. We have studied in particular the liver injury producedin vivo by three prototypical GSH depleting agents which undergo different fates in the liver cell: i) bromobenzene, that is metabolized by the microsomal monooxygenase system with consumption of NADPH (10–12); ii) allyl alcohol that is metabolized by the cytosolic enzyme alcohol dehydrogenase to acrolein and by aldehyde dehydrogenase to acrylic acid, with production of NADH (13,14); iii) and diethylmaleate which is mainly conjugated with GSH by GSH-transferases without previous metabolism (15).
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
E. A. Glende, Jr., and R. O. Recknagel, Biochemical basis for the in vitro pro-oxidant action of carbon tetrachloride, Exp. Mol. Pathol. 11:172 (1969).
T. F. Slater, “Free Radical Mechanisms in Tissue Injury” Pion Limited, London (1972).
M. Comporti, Lipid peroxidation and cellular damage in toxic injury, Lab. Invest. 53:599 (1985).
I. Anundi, J. Högberg, and A. H. Stead, Glutathione depletion in isolated hepatocytes: its relation to lipid peroxidation and cell damage, Acta Pharmacol. Toxicol. 45:45 (1979).
A. Wendel, S. Feuerstein, and K. H. Konz, Acute paracetamol intoxication of starved mice leads to lipid peroxidation in vivo, Biochem. Pharmacol. 28:2051 (1979).
A. Casini, M. Giorli, R. J. Hyland, A. Serroni, D. Gilfor, and J. L. Farber, Mechanisms of cell injury in the killing of cultured hepatocytes by bromobenzene, J. Biol. Chem. 257: 6721 (1982).
A. F. Casini, A. Pompella, and M. Comporti, Liver glutathione depletion induced by bromobenzene, iodobenzene, and diethylmaleate poisoning and its relation to lipid peroxidation and necrosis, Am. J. Pathol. 118:225 (1985).
A. F. Casini, E. Maellaro, A. Pompella, M. Ferrali, and M. Comporti, Lipid peroxidation, protein thiols and calcium homeostasis in bromobenzene-induced liver damage, Biochem. Pharmacol. 36:3689 (1987).
M. Comporti, Glutathione depleting agents and lipid peroxidation, Chem. Phys. Lipids 45:143 (1987).
D. J. Jollow, J. R. Mitchell, N. Zampaglione, and J. R. Gillette, Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite, Pharmacology 11:151 (1974).
J. R. Mitchell, and D. J. Jollow, Metabolic activation of drugs to toxic substances, Gastroenterology 68:392 (1975).
H. Thor, P. Moldéus, R. Hermanson, J. Högberg, D. J. Reed, and S. Orrenius, Metabolic activation and hepatotoxicity, Arch. Biochem. Biophys. 188:122 (1978).
J. M. Patel, W. P. Gordon, S. D. Nelson, and K. C. Leibman, Comparison of hepatic biotransformation and toxicity of allyl alcohol and (1,1–2H2)allyl alcohol in rats, Drug Metab. Dispos. 11:164 (1983).
E. Boyland, and L. F. Chasseaud, Enzyme-catalysed conjugation of glutathione with unsaturated compounds, Biochem. J. 104: 95 (1967).
C. C. Reddy, R. W. Scholz, C. E. Thomas, and E. J. Massaro, Evidence for a possible protein-dependent regeneration of vitamin E in rat liver microsomes, Ann. N. Y. Acad. Sci. 393:193 (1982).
P. B. McCay, E. K. Lai, S. R. Powell, and G. Breuggemann, Vitamin E functions as an electron shuttle for glutathione-depletion “free radical reductase” activity in biological membranes, Fed. Proc. 45:451 (1986).
J. E. Packer, T. F. Slater, and R. L. Willson, Direct observation of a free radical interaction between vitamin E and vitamin C, Nature (London) 278:737 (1979).
R. L. Willson, Free radical protection: why vitamin E, not vitamin C, ß-carotene or glutathione?, in: “Biology of Vitamin E. Ciba Foundation Symposium 101”, p. 19, Pitman, London (1983).
A. Pompella, E. Maellaro, A. F. Casini, M. Ferrali, L. Ciccoli, and M. Comporti, Measurement of lipid peroxidation in vivo: a comparison of different procedures, Lipids 22: 206 (1987).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Plenum Press, New York
About this chapter
Cite this chapter
Casini, A.F., Maellaro, E., Del Bello, B., Comporti, M. (1990). The Role of Vitamin E in the Hepatotoxicity by Glutathione Depleting Agents. In: Emerit, I., Packer, L., Auclair, C. (eds) Antioxidants in Therapy and Preventive Medicine. Advances in Experimental Medicine and Biology, vol 264. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5730-8_14
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5730-8_14
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5732-2
Online ISBN: 978-1-4684-5730-8
eBook Packages: Springer Book Archive