Skip to main content
PMC home page
British Journal of Experimental Pathology logoLink to British Journal of Experimental Pathology
. 1983 Aug;64(4):388–395.

Studies on the mechanism of glutathione prevention of carbon tetrachloride-induced liver injury.

N Gorla, E C de Ferreyra, M C Villarruel, O M de Fenos, J A Castro
PMCID: PMC2040791  PMID: 6615708

Abstract

The prior administration of reduced glutathione (GSH) partially prevents carbon tetrachloride (CCl4)-induced liver necrosis observed at 24 h after administration of the hepatotoxin. No prevention occurs when observations are made at 72 h. GSH pretreatment does not significantly modify the intensity of the covalent binding of CCl4 reactive metabolites to microsomal lipids or the intensity of the CCl4-induced lipid peroxidation process at either 1, 3 or 6 h after poisoning. GSH administration does not significantly prevent CCl4-induced cytochrome P-450 destruction or glucose 6 phosphatase activity depression. Pretreatment with GSH does not significantly modify the levels of CCl4 or i.p. administered CCl4 reaching the liver at 1, 3 or 6 h after intoxication. Pretreatment with GSH significantly prevents CCl4-induced decreases in body temperature. Results are interpreted as suggesting that GSH prevents CCl4-induced liver necrosis by changing the liver cell's response to injury rather than by modification of early events of the process such as lipid peroxidation or covalent binding of reactive metabolites.

Full text

PDF
388

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernacchi A. S., de Castro C. R., de Toranzo E. G., Marzi A., de Ferreyra E. C., de Fenos O. M., Castro J. A. Pyrazole prevention of CC14-induced ultrastructural changes in rat liver. Br J Exp Pathol. 1980 Oct;61(5):505–511. [PMC free article] [PubMed] [Google Scholar]
  2. Burk R. F. Protection by GSH against lipid peroxidation induced by ascorbate and iron in rat liver microsomes. Biochem Pharmacol. 1982 Feb 15;31(4):601–602. doi: 10.1016/0006-2952(82)90168-x. [DOI] [PubMed] [Google Scholar]
  3. Castro J. A., Cignoli E. V., De Castro C. R., De Fenos O. M. Prevention by cystamine of liver necrosis and early biochemical alterations induced by carbon tetrachloride. Biochem Pharmacol. 1972 Jan;21(1):49–57. doi: 10.1016/0006-2952(72)90249-3. [DOI] [PubMed] [Google Scholar]
  4. Castro J. A., De Ferreyra E. C., De Castro C. R., Díaz Gómez M. I., D'Acosta N., De Fenos O. M. Studies on the mechanism of cystamine prevention of several liver structural and biochemical alterations caused by carbon tetrachloride. Toxicol Appl Pharmacol. 1973 Jan;24(1):1–19. doi: 10.1016/0041-008x(73)90176-2. [DOI] [PubMed] [Google Scholar]
  5. Ciccoli L., Ferrali M., Casini A. F., Comporti M. Azione del glutatione ridotto sulla steatosi epatica da tetracloruro di carbonio: alcune considerazioni. Boll Soc Ital Biol Sper. 1981 Jul 15;57(13):1463–1469. [PubMed] [Google Scholar]
  6. Di Luzio N. R. Antioxidants, lipid peroxidation and chemical-induced liver injury. Fed Proc. 1973 Aug;32(8):1875–1881. [PubMed] [Google Scholar]
  7. Dianzani M. U., Gabriel L., Gravela E., Paradisi L. Interference of CCI4 metabolites with subcellular structures. Panminerva Med. 1976 Sep-Oct;18(9-10):310–319. [PubMed] [Google Scholar]
  8. Dianzani M. U., Ugazio G. Lipoperoxidation after carbon tetrachloride poisoning in rats previously treated with antioxidants. Chem Biol Interact. 1973 Feb;6(2):67–79. doi: 10.1016/0009-2797(73)90073-2. [DOI] [PubMed] [Google Scholar]
  9. Díaz Gómez M. I., de Castro C. R., D'Acosta N., de Fenos O. M., de Ferreyra E. C., Castro J. A. Species differences in carbon tetrachloride-induced hepatotoxicity: the role of CCl4 activation and of lipid peroxidation. Toxicol Appl Pharmacol. 1975 Oct;34(1):102–114. doi: 10.1016/0041-008x(75)90179-9. [DOI] [PubMed] [Google Scholar]
  10. ELLMAN G. L. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
  11. Gravela E., Dianzani M. U. Studies on the mechanism of CCl(4)-induced polyribosomal damage. FEBS Lett. 1970 Jul 29;9(2):93–96. doi: 10.1016/0014-5793(70)80321-0. [DOI] [PubMed] [Google Scholar]
  12. Gravela E., Gabriel L., Ugazio G. Protection by glutathione and propyl gallate on the impaired in vitro amino acid incorporation into liver microsomal protein of CCL 4 -poisoned rats. Biochem Pharmacol. 1971 Aug;20(8):2065–2070. doi: 10.1016/0006-2952(71)90407-2. [DOI] [PubMed] [Google Scholar]
  13. Griffith O. W., Meister A. Glutathione: interorgan translocation, turnover, and metabolism. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5606–5610. doi: 10.1073/pnas.76.11.5606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klaassen C. D., Plaa G. L. Comparison of the biochemical alterations elicited in livers from rats treated with carbon tetrachloride, chloroform, 1,1,2-trichloroethane and 1,1,1-trichloroethane. Biochem Pharmacol. 1969 Aug;18(8):2019–2027. doi: 10.1016/0006-2952(69)90299-8. [DOI] [PubMed] [Google Scholar]
  15. LARSON R. E., PLAA G. L. A CORRELATION OF THE EFFECTS OF CERVICAL CORDOTOMY, HYPOTHERMIA AND CATECHOLAMINES ON CARBON TETRACHLORIDE-INDUCED HEPATIC NECROSIS. J Pharmacol Exp Ther. 1965 Jan;147:103–111. [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Marchand C., McLean S., Plaa G. L. The effect of SKF 525A on the distribution of carbon tetrachloride in rats. J Pharmacol Exp Ther. 1970 Aug;174(2):232–238. [PubMed] [Google Scholar]
  18. Marchand C., McLean S., Plaa G. L., Traiger G. Protection by 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride against carbon tetrachloride hepatotoxicity. A possible mechanism of action. Biochem Pharmacol. 1971 Apr;20(4):869–875. doi: 10.1016/0006-2952(71)90049-9. [DOI] [PubMed] [Google Scholar]
  19. Marzi A., de Toranzo E. G., Castro J. A. Mechanism of chlorpromazine prevention of carbon tetrachloride-induced liver necrosis. Toxicol Appl Pharmacol. 1980 Jan;52(1):82–88. doi: 10.1016/0041-008x(80)90250-1. [DOI] [PubMed] [Google Scholar]
  20. McCay P. B., Gibson D. D., Hornbrook K. R. Glutathione-dependent inhibition of lipid peroxidation by a soluble, heat-labile factor not glutathione peroxidase. Fed Proc. 1981 Feb;40(2):199–205. [PubMed] [Google Scholar]
  21. McCray P. B., Gibson D. D., Fong K. L., Hornbrook K. R. Effect of glutathione peroxidase activity on lipid peroxidation in biological membranes. Biochim Biophys Acta. 1976 Jun 22;431(3):459–468. [PubMed] [Google Scholar]
  22. McLean A. E. The effect of diet and vitamin E on liver injury due to carbon tetrachloride. Br J Exp Pathol. 1967 Dec;48(6):632–636. [PMC free article] [PubMed] [Google Scholar]
  23. Pani P., Gravela E., Mazzarino C., Burdino E. On the mechanism of fatty liver in white phosphorus-poisoned rats. Exp Mol Pathol. 1972 Apr;16(2):201–209. doi: 10.1016/0014-4800(72)90035-4. [DOI] [PubMed] [Google Scholar]
  24. RECKNAGEL R. O., LITTERIA M. Biochemical changes in carbon tetrachloride fatty liver: concentration of carbon tetrachloride in liver and blood. Am J Pathol. 1960 May;36:521–531. [PMC free article] [PubMed] [Google Scholar]
  25. Rao K. S., Recknagel R. O. Early incorporation of carbon-labeled carbon tetrachloride into rat liver particulate lipids and proteins. Exp Mol Pathol. 1969 Apr;10(2):219–228. doi: 10.1016/0014-4800(69)90041-0. [DOI] [PubMed] [Google Scholar]
  26. Rechnagel R. O., Glende E. A., Jr Carbon tetrachloride hepatotoxicity: an example of lethal cleavage. CRC Crit Rev Toxicol. 1973 Nov;2(3):263–297. doi: 10.3109/10408447309082019. [DOI] [PubMed] [Google Scholar]
  27. Recknagel R. O. Carbon tetrachloride hepatotoxicity. Pharmacol Rev. 1967 Jun;19(2):145–208. [PubMed] [Google Scholar]
  28. STERKEL R. L., SPENCER J. A., WOLFSON S. K., Jr, WILLIAMS-ASHMAN H. G. Serum isocitric dehydrogenase activity with particular reference to liver disease. J Lab Clin Med. 1958 Aug;52(2):176–184. [PubMed] [Google Scholar]
  29. Schenkman J. B., Remmer H., Estabrook R. W. Spectral studies of drug interaction with hepatic microsomal cytochrome. Mol Pharmacol. 1967 Mar;3(2):113–123. [PubMed] [Google Scholar]
  30. Slater T. F. Necrogenic action of carbon tetrachloride in the rat: a speculative mechanism based on activation. Nature. 1966 Jan 1;209(5018):36–40. doi: 10.1038/209036a0. [DOI] [PubMed] [Google Scholar]
  31. Smuckler E. A., Arcasoy M. Structural and functional changes of the endoplasmic reticulum of hepatic parenchymal cells. Int Rev Exp Pathol. 1969;7:305–418. [PubMed] [Google Scholar]
  32. Torrielli M. V., Gabriel L., Dianzani M. U. Ethanol-induced hepatotoxicity; experimental observations on the role of lipid peroxidation. J Pathol. 1978 Sep;126(1):11–25. doi: 10.1002/path.1711260103. [DOI] [PubMed] [Google Scholar]
  33. Villarruel M. C., Díaz Gómez M. I., Castro J. A. The nature of the in vitro irreversible binding of carbon tetrachloride to microsomal lipids. Toxicol Appl Pharmacol. 1975 Jul;33(1):106–114. doi: 10.1016/0041-008x(75)90249-5. [DOI] [PubMed] [Google Scholar]

Articles from British journal of experimental pathology are provided here courtesy of Wiley

RESOURCES