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Protection from N-Nitrosodimethylamine Mediated Liver Damage by Indole-3-Carbinol, and Correlation with Nucleophilic Index Value

  • H. G. Shertzer
  • M. L. Berger
  • M. W. Tabor

Abstract

Indole-3-carbinol (I-3-C), a normal constituent of the human diet via cruciferous vegetables, was examined for its ability to protect mice against 24-hour N-nitrosodimethylamine (NDMA)-mediated hepatotoxicity. NDMA (20 mg/kg body weight) alone produced extensive hemorrhagic and centrolobular necrotic lesions, with a necrotic severity index of 3.0 ± 0.4 (scale of 0-5). Treatment with 50 mg/kg body weight of I-3-C by gavage, 1 hour prior to NDMA, substantially protected against hemorrhagic lesions. Furthermore, I-3-C lowered the NDMA-mediated tissue necrotic index to 1.5 ± 0.3, by reducing the extent of tissue necrosis rather than the severity in the necrotic region. Release of liver enzymes into the blood correlated with the histopathology; I-3-C reduced NDMA-mediated elevated activities of plasma alanine transaminase and ornithine transcarbamylase by 84% and 51.3%, repectively (Table 1). Plasma activities of these enzymes were used as indicators of hepatotoxicity. Although no changes in liver non-protein sulfhydryls were evident at 24 hours after NDMA, ascorbate levels were reduced to 40% of controls values. Treatment with I-3-C prior to NDMA prevented this decline in tissue ascorbate concentrations.

Keywords

Rainbow Trout Ethyl Acetate Extract Cruciferous Vegetable Necrotic Region Ornithine Transcarbamylase 
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.

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References

  1. 1.
    H.G. Shertzer, Indole-3-carblnol protects against covalent binding of benzo(a)pyrene and N-nitrosodimethylamine Metabolites to mouse liver macromolecules. Chem.-Biol. Interact. 48, 81–90 (1984).PubMedCrossRefGoogle Scholar
  2. 2.
    J. Green, Vitamin E and the biological antioxidant theory. Ann. N.Y. Acad. Sci. 203, 29–44 (1972).PubMedCrossRefGoogle Scholar
  3. 3.
    H.G. Shertzer, M.P. Niemi, F.A. Reitman, M.L. Berger, B.L. Myers, and M.W. Tabor, Protection against carbon tetrachloride hepatotoxicity by pretreatment with indole-3-carbinol. Exp. Mol. Pathol. 46, 180–189 (1987).PubMedCrossRefGoogle Scholar
  4. 4.
    G.S. Bailey, D. Goeger, J.D. Hendricks, J.E. Nixon and N.E. Pawlowski, Indole-3-carbinol promotion and inhibition of aflatoxin B, carcinogenesis in rainbow trout. Proc. Am. Assoc. Cancer Res. 26, 115 (1985).Google Scholar
  5. 5.
    J.E. Nixon, J.D. Hendricks, N.E. Pawlowski, C.B. Pereira, R.O. Sinnhuber and G.S. Bailey, Inhibition of aflatoxin B1 carcinogenesis in rainbow trout by flavone and indole compounds. Carcinogenesis 5, 615–619 (1984).PubMedCrossRefGoogle Scholar
  6. 6.
    L.W. Wattenberg and W.D. Loub, Inhibition of polycyclic aromatic hydrocarbon-induced neoplasic by naturally occurring indoles. Cancer Res. 38, 1410–1413 (1978).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • H. G. Shertzer
    • 1
  • M. L. Berger
    • 2
  • M. W. Tabor
    • 1
  1. 1.Department of Environmental Health (Liver Study Unit, Divivision of Digestive Diseases)University Cincinnati Medical CenterCincinnatiUSA
  2. 2.Department of International Medicine (Liver Study Unit, Divivision of Digestive Diseases)University Cincinnati Medical CenterCincinnatiUSA

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