The Liver as Origin and Target of Reactive Intermediates Exemplified by the Progesterone Derivative, Cyproterone Acetate

Since the middle of the last century it is known that chemicals can cause liver injury (cf. Zimmerman, 1978). In 1860, a severe fatty liver in man was ascribed to phosphorous intoxication. During the first half of the 20th century several hepatotoxins have been extensively studied and in the second half of this century it became clear that in many cases enzymatically ‘activated’ metabolites of xenobiotics are responsible for the toxic effects observed (cf. Zimmerman, 1978; Hinson et al., 1994). The liver was found to express the highest concentrations and greatest variety of xenobiotic metabolizing enzymes in the body (cf. Zimmerman, 1978; Watkins, 1990). This high metabolic capacity turned out to be a primary cause of the liver specificity of toxic xenobiotics. Chemically induced liver damage may have three main manifestations (Fig. 1).