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MARÍA JOSÉ GÓMEZ-LECHÓN y MARÍA TERESA DONATO AN. R. ACAD. NAC. FARM.

FIGURE 4. Mechanisms of drug hepatotoxicity. Different mechanisms can be
involved in hepatocyte toxicity: Mitochondrion is a frequent target of hepatotoxic

drugs and the alteration of its function has immediate effects on the energetic
balance of cells (depletion of ATP). Lipid peroxidation, oxidative stress, alteration
of Ca2+ homeostasis and covalent binding to cell macromolecules are the molecular

mechanisms more frequently involved in the toxicity of xenobiotics.

The monitoring of gene expression of cells exposed to toxic
xenobiotics (toxicogenomics), has gained great popularity among
researchers (61-63). The ease with which thousands of genes can be
measured has led most of the scientists to register changes of as
many genes as possible with the hope that an in-depth biostatistical
analysis would reveal which of that gene were clearly linked to toxic
events. It is hoped that through a better understanding of cellular
mechanisms of toxicity, combined with mechanistically directed
toxicogenomic analysis, the accuracy and predictivity of in vitro
screening for toxicants could be greatly improved.

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