Advertisement

Liver Endoplasmic Reticulum: Target Site of Halocarbon Metabolites

  • Edward S. Reynolds
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 84)

Abstract

Initial injury produced by exposure of rats to carbon tetrachloride, halothane, vinyl chloride or trichloroethylene appears to involve the endoplasmic reticulum. First, there is dispersion of the ergastoplasm, then vacuolization and degranulation of the rough endoplasmic reticulum with concomitant retraction of the smooth endoplasmic reticulum into tightly clumped tubular aggregates. In addition, membranes in these tubular aggregates seem to undergo supra-molecular disassembly. Along with this structural disorganization, functional capacity of the organelle diminishes. Activation of these halocarbons to toxic species by functional elements of the endoplasmic reticulum is indicated by the enhancement of their toxicity by pretreatment with chemicals which induce components of the mixed function oxidase system and by the formation of certain metabolites and/or covalently bound products. Insight into the molecular mechanisms of membrane injury brought about by these halocarbon hepatotoxins has been provided by the characterization of chemical changes produced, such as increased lipid diene conjugate content, and the patterns of enzyme deactivation.

Keywords

Endoplasmic Reticulum Carbon Tetrachloride Diene Conjugation Mixed Function Oxidase Pretreated Animal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    BIDLACK, W.R.: Ph.D. Dissertation (1972) p. 94.Google Scholar
  2. 2.
    BOLIAND, J.L. and KOCH, H.P.: J. Chem. Soc. (1945) p. 445.Google Scholar
  3. 3.
    BROWN, B.R., Jr.: Anesthesiology 36 (1972) 458.PubMedCrossRefGoogle Scholar
  4. 4.
    BUTIER, T.C.: J. Pharmacol. Exptl. Therap. 134 (1961) 311.Google Scholar
  5. 5.
    CALLIGARO, A., CONGIU, L., TOCCO, L., and VANNINI, V.: La Sperimentale 121 (1971) 121.Google Scholar
  6. 6.
    CARLSON, G.P.: Res. Comm. Chem. Pathol. Pharmacol. 7 (1974) 637.Google Scholar
  7. 7.
    CARLSON, G.P.: Toxicology 5 (1975) 69.PubMedCrossRefGoogle Scholar
  8. 8.
    COMPORTI, M., IANDUCCI, G. and RAJA, F.: Separatum Experi-entia 27 (1971) 1155.Google Scholar
  9. 9.
    DAHLE, L.K., HILL, E.G., and HOLMAN, R.T.: Arch. Biochem. Biophys. 98 (1962) 253.PubMedCrossRefGoogle Scholar
  10. 10.
    DIAZ-GOMEZ, M.I., CASTRO, J.A., DEFERREYRA, E.C., D’ACOSTA, N., DECASTRO, C.R.: Toxicol. Appl. Pharmacol. 25 (1973) 534.PubMedCrossRefGoogle Scholar
  11. 11.
    DREW, R.T., HARPER, C., GUPTA, B.N., and TALLEY, F.A.: Envirn. Health Persp. 11 (1975) 235.CrossRefGoogle Scholar
  12. 12.
    FOTLER, J.S.L.: Brit. J. Pharmacol. 37 (1969) 733.Google Scholar
  13. 13.
    GLENDE, E.A., Jr., and RECKNAGEL, R.O.: Fed. Proc. 33 (1974) 219.Google Scholar
  14. 14.
    GOPINATH, C., and FORD, E.J.H.: J. Pathol. 110 (1973) 333.CrossRefGoogle Scholar
  15. 15.
    GREGORY, N.L.: Nature 212 (1966) 1460.PubMedCrossRefGoogle Scholar
  16. 16.
    HÖGBERG, J., BERGSTRAND, A., and JAKOBSSON, S.V.: Europ. J. Biochem. 37 (1973) 51.PubMedCrossRefGoogle Scholar
  17. 17.
    HOLMAN, R.T.: Progress in the Chemistry of Fats and Other Lipids, p. 51 (Holman, R.T., Landsberg, O., Malkin, T., Eds) academic Press, New York (1954).Google Scholar
  18. 18.
    JAEGER, R.J., REYNOLDS, E.S., CONOLLY, R.B., MOSLEN, M.T., SZABO, S., and MURPHY, S.D.: Nature 252 (1974) 724.PubMedCrossRefGoogle Scholar
  19. 19.
    KIAASSEN, C.D. and PUA, G.L.: Biochem. Pharmacol. 18 (1969) 2019.CrossRefGoogle Scholar
  20. 20.
    KOCH, R.R., GLENDE, E.A., JR., RECKNAGEL, R.O.: Biochem. Pharmacol. 23 (1974) 2907.PubMedCrossRefGoogle Scholar
  21. 21.
    MOSLEN, M.T., REYNOLDS, E.S., SZABO, S.: Fed. Proc. 35 (1976) 375.Google Scholar
  22. 22.
    MOSLEN, M.T., REYNOLDS, E.S., SZABO, S.: Biochem. Pharmacol. (in press).Google Scholar
  23. 23.
    MOSLEN, M.T., REYNOLDS, E.S., BOOR, P.J., SZABO, S. (in preparation),Google Scholar
  24. 24.
    PAUL, B.B., and RUBINSTEIN, D.: J. Pharmacol. Exptl. Therap. 141 (1963) 141.Google Scholar
  25. 25.
    PEDERSON, T.C. and AUST, S.D.: Biochem. Biophys. Res. Comm. 48 (1972) 789.PubMedCrossRefGoogle Scholar
  26. 26.
    RAO, K.S. and RECKNAGEL, R.O.: Exptl. Molec. Pathol. 9 (1968) 271.CrossRefGoogle Scholar
  27. 27.
    RAO, K.S. and RECKNAGEL, R.O.: Exptl. Molec. Pathol. 10 (1969) 219.CrossRefGoogle Scholar
  28. 28.
    RECKNAGEL, R.O., GLENDE, E.A., JR.: Crit. Rev. Toxicol. 2 (1973) 263.CrossRefGoogle Scholar
  29. 29.
    REINER, O., ATHANASSOPOULOUS, S., HELLMER, K.H., MURRAY, R.E., and UEHLEKE, H.: Arch. Toxicol. 29 (1972) 219.CrossRefGoogle Scholar
  30. 30.
    REYNOLDS, E.S.: Pharmacol. Exptl. Therap. 155 (1967) 117.Google Scholar
  31. 31.
    REYNOLDS, E.S., and MOSLEN, M.T.: Biochem. Pharmacol. 23 (1974) 189.PubMedCrossRefGoogle Scholar
  32. 32.
    REYNOLDS, E.S., and MOSLEN, M.T.: Biochem. Pharmacol. 24 (1975) 2075.PubMedCrossRefGoogle Scholar
  33. 33.
    REYNOLDS, E.S. and REE, H.J.: Lab. Invest. 25 (1971) 269.PubMedGoogle Scholar
  34. 34.
    REYNOLDS, E.S., REE, H.J., MOSLEN, M.T.: Lab. Invest. 26 (1972) 290.PubMedGoogle Scholar
  35. 35.
    REYNOLDS, E.S., MOSLEN, M.T., SZABO, S.: Fed. Proc. 38 (1976) 376.Google Scholar
  36. 36.
    REYNOLDS, E.S., MOSLEN, M.T., SZABO, S., JAEGER, R.J.: Res, Comm. Chem. Pathol. Pharmacol 12 (1975) 685.Google Scholar
  37. 37.
    REYNOLDS, E.S., MOSLEN, M.T., SZABO, S., JAEGER, R.J., MURPHY, S.D.: Am. J. Pathol. 81 (1975) 219.PubMedGoogle Scholar
  38. 38.
    SEAWRIGHT, A.A. and MCLEAN, A.E.M.: Biochem. J. 105 (1967) 1055.PubMedGoogle Scholar
  39. 39.
    SELL, D.A., and REYNOLDS, E.S.: J. Cell Biol. 41 (1969) 736.PubMedCrossRefGoogle Scholar
  40. 40.
    SGOUTAS, D.S.: Metabolism 16 (1967) 382.PubMedCrossRefGoogle Scholar
  41. 41.
    SLATER, T.F. and SAWYER, B.C.: Biochem. J. 111 (1969) 317.PubMedGoogle Scholar
  42. 42.
    SLATER, T.F. and SAWYER, B.C.: Biochem. J. 123 (1971) 805, 815 and 823.PubMedGoogle Scholar
  43. 43.
    SMUCKER, E.A. and ARCASOY, M.: Int. Rev. Exptl. Pathol. 7 (1969) 305.Google Scholar
  44. 44.
    STENGER, R.J. and JOHNSON, E.A.: Proc. Soc. Exptl. Biol. Med. 140 (1972) 1319.Google Scholar
  45. 45.
    STRIPP, B., HAMRICK, M.E. and GILLETTE, J.R.: Biochem. Pharmacol, 21 (1972) 745.PubMedCrossRefGoogle Scholar
  46. 46.
    TAM, B.K. and MCCAY, P.B.: J. Biol. Chem. 245 (1970) 2295.PubMedGoogle Scholar
  47. 47.
    UEHLEKE, H., HELLMER, K.H., TABARELLI, S.: Xenobiotica 3 (1973) 1.PubMedCrossRefGoogle Scholar
  48. 48.
    UEHLEKE, H., HELLMER, K.H., and TABARELLI-POPLAWSKI, S.: Natmyn-Schmiedeberg’s Arch. Pharmacol. 279 (1973) 39.Google Scholar
  49. 49.
    VAN DYKE, R.A., and GANDOLFI, A.J.: Drug. Met. Disp. 4 (1976) 40.Google Scholar
  50. 50.
    WIDGER, L.A., GANDOLFI, A.J., and VAN DYKE, R.A.: Anesthesiology 44 (1976) 197.PubMedCrossRefGoogle Scholar
  51. 51.
    WILLS, E.D.: Biochem. J. 123 (1971) 983.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Edward S. Reynolds
    • 1
    • 2
  1. 1.Department of PathologyPeter Bent Brigham Hospital and Harvard Medical School BostonMassachusettsUSA
  2. 2.Harvard Medical School BostonMassachusettsUSA

Personalised recommendations