Overview of Hepatotoxicity

Sharon A. Meyer1

1 University of Louisiana—Monroe, Monroe, Louisiana
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 14.1
DOI:  10.1002/0471140856.tx1401s08
Online Posting Date:  August, 2001
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This overview presents some of the salient features of liver biology and physiology that form the basis for a variety of experimental tools that are used for the study of chemical histopathology. Prevalence and risk of heptatoxicity are examined among a subset of chemicals from the EPA IRIS database. The goal is to provide an objective assessment of the magnitude of the problem of chemically‚Äźinduced hepatotoxicity and contextual background against which the diversity of responses of the liver to toxicants and the analytical methods available for their study can be appreciated.

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Table of Contents

  • Frequency of Chemically Induced Hepatotoxicity
  • Liver Function in Susceptibility to Hepatotoxicant Targeting
  • Types of Toxic Responses of Liver and Their Assessment
  • Conclusion
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Literature Cited

Literature Cited
   Arias, I.M., Boyer, J.L., Fausto, N., Jakoby, W.B., Schachter, D., and Shafritz, D.A. 1994. The Liver. Biology and Pathobiology. Raven Press, New York.
   Chhabra, R.S., Huff, J.E., Schwetz, B.W., and Selkirk, J. 1990. An overview of prechronic and chronic toxicity/carcinogenicity experimental study designs and criteria used by the National Toxicology Program. Environ. Hlth. Persp. 86:313‐321.
   Cullen, J.M. and Marion, P.L. 1996. Non‐neoplastic liver disease associated with chronic ground squirrel hepatitis viral infection. Hepatology 23:1324‐1329.
   Dragan, Y.P., Rizvi, T., Xu, Y.H., Hully, J.R., Bawa, N., Campbell, H.A., Maronpot, R.R., and Pitot, H.C. 1991. An initiation‐promotion assay in rat liver as a potential complement to the 2‐year carcinogenesis bioassay. Fundam. Appl. Toxicol. 16:525‐547.
   Gupta, S., Rajvanshi, P., Sokhi, R.P., Vaidya, S., Irani, A.N., and Gorla, G.R. 1999. Position‐specific gene expression in the liver lobule is directed by the microenvironment and not by the previous cell differentiation state. J. Biol. Chem. 274:2157‐2165.
   Jaeschke, H., Smith, C.W., Clemens, M.G., Ganey, P.E., and Roth, R.A. 1996. Mechanisms of inflammatory liver injury: Adhesion molecules and cytotoxicity of neutrophils Toxicol. Appl. Pharmacol. 139:213‐226.
   Liu, X., Chism, J.P., LeCluyse, E.L., Brouwer, K.R., and Brouwer, K.L. 1999. Correlation of biliary excretion in sandwich‐cultured rat hepatocytes and in vivo in rats. Drug Metab. Dispos. 27:637‐644.
   Rogler, C.E., Rogler, L.E., Yang, D., Breiteneder‐Gerleer, S., Gong, S., and Haiping, W. 1995. Contributions of hepadnavirus research to our understanding of hepatocarcinogenesis. In Liver Regeneration and Carcinogenesis. Molecular and Cellular Mechanisms (R.L. Jirtle, ed.) pp. 113‐140. Academic Press, San Diego.
   Slattery, J.T., Nelson, S.D., and Thummel, K.E. 1996. The complex interaction between ethanol and acetaminophen. Clin. Pharmacol. Ther. 60:241‐246.
   Tennant, B.C. 1999. Assessment of hepatic function. In The Clinical Chemistry of Laboratory Animals (W.F. Loeb and R.W. Quimby, eds.) pp. 501‐517. Taylor & Francis, Philadelphia.
   Thurman, R.G., Bradford, B.U., Iimuro, Y., Frakenberg, M.V., Knecht, K.T., Connor, H.D., Adachi, Y., Wall, C., Areetl, G.E., Raleigh, J.A., Forman, D.T., and Mason, R.P. 1999. Mechanisms of alcohol‐induced hepatotoxicity: Studies in rats. Front. Biosci. 4:e42‐46.
   Zimmerman, H.J. 1998. Drug‐induced hepatic disease. In Toxicology of the Liver, 2nd ed. (G.L. Plaa and W.R. Hewitt, eds.) pp. 3‐60. Taylor & Francis, Washington, D.C.
Key References
   Arias et al., 1994. See above.
  A comprehensive reference book that details much of the biological and physiological background for understanding function of the normal liver and its impairment in disease.
   McCuskey, R.S. and Earnest, D.L. (eds.) 1997. Comprehensive Toxicology, Vol. 9. Hepatic and Gastrointestinal Toxicology (I.G. Sipes, C.A. McQueen, and A.J. Gandolfi, eds.) Pergamon/Elsevier, New York.
  Two collections of review chapters devoted to toxic effects in the liver. The first includes chapters focused upon chemical‐specific effects and the latter focuses on systems and mechanisms of toxic effects.
   Plaa, G.L. and Hewitt, W.R., eds. 1998. Toxicology of the Liver, 2nd ed. Taylor & Francis, Washington, D.C.
Internet Resources
  The Integrated Risk Information System home page from the EPA.
  ChemRTK and HPV Challenge Program Chemical List from the EPA's Office of Pollution Prevention and Toxics (OPPTS).
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