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Toxicant-Induced Liver Injury

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Molecular Pathology of Liver Diseases

Part of the book series: Molecular Pathology Library ((MPLB,volume 5))

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Abstract

Chemical- and drug-induced liver injury is a significant problem in clinical practice and during drug development. Many drugs fail during development due to acute hepatotoxicity. However, a substantial number of drugs currently on the market or already withdrawn have the potential to cause liver injury [1, 2]. Most of these drug-induced hepatotoxicities are idiosyncratic and the mechanisms of cell injury are not well understood [1, 2]. However, currently the most frequent cause of drug-induced liver failure in the United States and many other countries is acetaminophen (APAP) overdose [3]. In contrast to many other drugs on the market, acetaminophen causes acute liver injury in a dose-dependent manner. Relevant animal models are available and many aspects of the pathophysiology have been studied [4]. In addition to its clinical relevance, APAP is widely used as a model liver toxin to evaluate potential hepatoprotective compounds and therapeutic strategies. Therefore, this review will focus on mechanisms of drug-induced liver injury using mainly APAP as the best studied example. However, there are reviews focusing on other compounds not covered in this chapter including many environmental hepatotoxicants, for example, microcystins [5], herbal extracts [6], metals (e.g., iron, copper, cadmium) [7, 8], and specific chemicals such as carbon tetrachloride [9].

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  1. Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA

    Hartmut Jaeschke

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  1. School of Medicine, Dept. Pathology, University of Pittsburgh, 200 Lothrop Street, S421-BST, Pittsburgh, 15261, Pennsylvania, USA

    Satdarshan P. S. Monga

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Jaeschke, H. (2011). Toxicant-Induced Liver Injury. In: Monga, S. (eds) Molecular Pathology of Liver Diseases. Molecular Pathology Library, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7107-4_42

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