Publication Details

Jones, A. L. (2006). Hepatotoxicity. In J. H. Duffus & H. G.J.. Worth (Eds.), Fundamental Toxicology (pp. 189-197). Cambridge, UK: The Royal Society of Chemisty.


Many potentially toxic substances enter the body via the gastrointestinal tract (gut). As the blood supply from the gastrointestinal tract, through the portal vein, drains into the liver, the liver comes into contact with the potentially toxic substances, and this exposure will often be at a higher concentration than that received by other tissues. The liver is essential for the metabolic disposal of virtually all xenobiotics (foreign substances). This process is mostly achieved without injury to the liver itself or to other organs. A few compounds such as carbon tetrachloride are toxic themselves and/or produce metabolites that cause liver injury in a dose-dependent fashion. However, most agents cause liver injury only under special circumstances when toxic substances accumulate. Factors contributing to the build-up of such toxic substances include genetic enzyme variants (metabolizing enzymes with altered function due to gene defects), which allow greater formation of the harmful metabolite, and induction (greater production) of an enzyme that produces more than the usual quantity of [Oxic substance. There may also be accumulation of toxic substances by interference with regular non-toxic metabolic pathways by substrate competition for enzyme, e.g. ethanol and trichloroethylene, or depletion of substrates used to metabolize the toxins or prevent toxic injury, e.g. glutathione.

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