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Alteration of Chloroform-Induced Nephrotoxicity by Exogenous Ketones

  • William R. Hewitt
  • Esther M. Brown
  • Michel G. Côté
  • Gabriel L. Plaa
  • Hiroakil Miyajima

Abstract

Chemical-induced potentiation of haloalkane toxicity is not a novel observation. While potentiation of liver injury is the most frequently examined aspect of this problem (Hewitt et al., 1980a), a number of reports have indicated that the renal injury produced by various haloalkanes can be exacerbated by prior exposure to a number of different compounds. For example, Klaassen and Plaa (1966) demonstrated that a single 5 g/kg dose of ethanol significantly increased the chloroform (CHCl3)- and 1,1,2-trichloroethane-induced depression of mouse kidney phenolsulfonephthalein excretion. Subsequently, Watrous and Plaa (1971) found that two additional alcohols, isobutyl and isoamyl alcohol, potentiated CHCl3-induced nephrotoxicity in mice. However, these investigators also found that seven other alcohols did not increase the renal damage produced by CHCl3. Recently, Kluwe and Hook (1978) and Kluwe et al (1979) found that mice fed polybrominated biphenyls were markedly more susceptible to the nephrotoxic effects of CHCl3, carbon tetrachloride, trichloroethylene, and 1,1,2-trichloroethane. In contrast, pretreatment of mice with phénobarbital had no effect on CHCl3-induced nephrotoxicity, whereas pretreatment with 3-methylcholanthrene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, or polychlorinated biphenyls actually reduced the renal toxicity of CHCl3 (Kluwe et al., 1978).

Keywords

Blood Urea Nitrogen Renal Damage Environmental Toxicant Carbonyl Moiety Renal Cortical Slice 
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. Bus, J. S., White, E. L., and Barrow, C. S., 1979, Disposition of n-hexane in rats after single and repeated inhalation exposure, Toxicol Appl. Pharmacol. 48:A167.Google Scholar
  2. Couri, D., Abdel-Rahman, M. S., and Hetland, L. B., 1976, Biotransformation of hexane and methyl n-butyl ketone, Toxicol Appl Pharmacol 37:124.Google Scholar
  3. DiVincenzo, G. D., Kaplan, C. J., and Dedinas, J., 1976, Characterization of the metabolites of methyl n-butyl ketone in guinea pig serum and their clearance, Toxicol Appl Pharmacol 36:511.CrossRefGoogle Scholar
  4. Dolara, P., Franconi, F., and Basosi, D., 1978, Urinary excretion of some n-hexane metabolites, Pharmacol Res. Commun. 10:503.CrossRefGoogle Scholar
  5. Hewitt, W. R., Miyajima, H., Côté, M. G., and Plaa, G. L., 1979, Acute alteration of chloroform-induced hepato- and nephrotoxicity by mirex and Kepone, Toxicol Appl. Pharmacol 48:509.CrossRefGoogle Scholar
  6. Hewitt, W. R., Miyajima, H., Côté, M. G., and Plaa, G. L., 1980a, Modification of haloalkane-induced hepatotoxicity by exogenous ketone and metabolic ketosis, Fed. Proc. 39:3118.Google Scholar
  7. Hewitt, W. R., Miyahima, H., Côté, M. G., and Plaa, G. L., 1980b, Acute alteration of chloroform-induced hepato- and nephrotoxicity by n-hexane, methyl n-butyl ketone and 2,5-hexanedione, Toxicol. Appl. Pharmacol 53:230.CrossRefGoogle Scholar
  8. Ilett, K. F., Reid, W. D., Sipes, I. G., and Krishna, G., 1973, Chloroform toxicity in mice: Correlation of renal and hepatic necrosis with covalent binding of metabolites to tissue macromolecules, Exp. Mol. Pathol 19:215.CrossRefGoogle Scholar
  9. Klaassen, C. D.,and Plaa, G. L., 1966, Relative effects of various chlorinated hydrocarbons on liver and kidney function in mice, Toxicol. Appl. Pharmacol 9:139.CrossRefGoogle Scholar
  10. Kluwe, W. M., and Hook, J. B., 1978, Polybrominated biphenyl-induced potentiation of chloroform toxicity, Toxicol Appl. Pharmacol. 45:861.CrossRefGoogle Scholar
  11. Kluwe, W. M., McCormack, K. M., and Hook, J. B., 1978, Selective modification of the renal and hepatic toxicities of chloroform by induction of drug-metabolizing enzyme systems in kidney and liver, J. Pharmacol. Exp. Ther. 207:566.Google Scholar
  12. Kluwe, W. M., Hermann, C. L., and Hook, J. B., 1979, Effects of dietary polychlorinated biphenyls and polybrominated biphenyls on the renal and hepatic toxicities of several chlorinated hydrocarbon solvents in mice, J. Toxicol. Environ. Health 5:605.CrossRefGoogle Scholar
  13. Watrous, W. M., and Plaa, G. L., 1971, The potentiation of CHCl3-induced nephrototoxicity by some aliphatic alcohols in mice, Pharmacologist 13:227.Google Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • William R. Hewitt
    • 1
    • 2
  • Esther M. Brown
    • 1
  • Michel G. Côté
    • 3
  • Gabriel L. Plaa
    • 3
  • Hiroakil Miyajima
    • 3
  1. 1.Department of Veterinary Anatomy-PhysiologyCollege of Veterinary Medicine, University of Missouri-ColumbiaColumbiaUSA
  2. 2.Department of PharmacologySchool of Medicine, University of Missouri-ColumbiaColumbiaUSA
  3. 3.Département de Pharmacologie, Faculté de MédecineUniversité de MontréalMontréalCanada H3C 3J7

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