Membrane Stabilization as a Fundamental Event in the Mechanism of Chemoprotection Against Chemical Intoxication

  • Howard G. Shertzer
  • Malcolm Sainsbury
  • Marc L. Berger
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


Elucidation of the mechanisms involved in chemical intoxication is difficult due to the concurrence of multiple cellular events. The major physiological consequences of toxicant-induced injury are organellar dysfunctions, including plasma membrane leakiness, loss of mitochondrial energy homeostasis, limited or pervasive autolysis due to release of lysozomal proteolytic enzymes, nucleic acid damage, and impairment of endoplasmic reticular functions including protein turnover, biotransformation, subcellular packaging and calcium homeostasis (Kaplowitz et al., 1986; Popper & Keppler, 1986). Often organellar associated events are correlated with biochemical events, such as alterations in thiol status, ion homeostasis, ATP levels or lipid peroxidation (Jones et al., 1986; Mitchell et al., 1982; Brattin et al., 1985; Comporti, 1989). In this report we have examined the physicochemical properties of 10 hydrophobic antioxidants that protect against chemical toxicity in isolated rat hepatocytes. Protection is shown to be correlated with both radical quenching and membrane stabilization properties of these compounds.


Lipid Peroxidation Osmotic Fragility Radical Quenching Endoplasmic Reticular Function Jefferson Medical College 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Brattin, W.J., Glende, E.A. Jr., and Recknagel, R.0. (1985). Pathological mechanisms in carbon tetrachloride hepatotoxicity. J. Free Radicals Biol. Med. 1, 27–38.CrossRefGoogle Scholar
  2. Comporti, M. (1989). Three models of free radical-induced cell injury. Chem.-Biol. Interactions 72, 1–56.CrossRefGoogle Scholar
  3. Jones, T.W., Thor, H., and Orrenius, S. (1986). In vitro studies of mechanisms of cytotoxicity. Fd. Chem. Toxicol. 24, 769–773.Google Scholar
  4. Kaplowitz, N., Aw, T.Y., Simon, F.R., and Stolz, A. (1986). Drug-induced hepatotoxicity. Ann. Int. Med. 104, 826–839.PubMedGoogle Scholar
  5. Mitchell, J.R., Corcoran, G.B., Hughes, H., Lauterburg, B.H., and Smith, C.V. (1982). Acute lethal liver injury caused by chemically reactive metabolites. In Organ-Directed Toxicity: Chemical Indices and Mechanisms ( S.S. Brown and D.S. Davies, Eds.), pp. 117–129. Pergamon Press, NY.Google Scholar
  6. Popper, H., and Keppler, D. (1986). Networks of interacting mechanisms of hepatocellular degeneration and death. Prog. Liv. Dis. 8, 209–235.Google Scholar
  7. Shertzer, H.G., Niemi, M.P., Reitman, F.A., Berger, M.L., Myers, B.L., and Tabor, M.W. (1987a). Protection against carbon tetrachloride hepatotoxicity by pretreatment with indole-3-carbinol. Exptl. Mo/ec. Pathol. 46, 180–189.Google Scholar
  8. Shertzer, H.G., Tabor, M.W., and Berger, M.L. (1987b). Protection from N-nitrosodimethylamine mediated liver damage by indole-3-carbinol. Exptl. Malec. Pathol. 47, 211–218.Google Scholar
  9. Shertzer, H.G., Tabor, M.W., and Berger, M.L. (1988). Intervention in free radical mediated hepatotoxicity and lipid peroxidation by indole-3-carbinol. Biochem. Pharmacol. 37, 333–338.CrossRefGoogle Scholar
  10. Shertzer H.G., and Sainsbury, M. (1988). Protection against carbon tetrachloride hepatotoxicity by 5,10-dihydroindeno[1,2-b]indole, a potent inhibitor of lipid peroxidation. Fd. Chem. Toxicol. 26, 517–522.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Howard G. Shertzer
    • 1
  • Malcolm Sainsbury
    • 2
  • Marc L. Berger
    • 3
  1. 1.University of Cincinnati Medical CenterCincinnatiUSA
  2. 2.University of BathBathUK
  3. 3.Jefferson Medical CollegePhiladelphiaUSA

Personalised recommendations