Liver toxicity

A range of contaminants including carcinogens, metals, biotoxins, and persistent organic pollutants injure the livers of fishes, and, although some mechanisms of liver injury are unique to fish, often hepatic injury in these aquatic vertebrates arises from mechanisms similar to those observed in mammals. Development and approval of pharmaceuticals, personal-care products, and cosmetics and the identification of occupational safety risk factors have led to an abundance of information regarding hepatic injury in mammals. For fish, no such large-scale programs have served to further understanding of hepatic toxicology. For students of the toxicology of fishes, it is important to review some of the interests that have led to the current state of our knowledge regarding toxicity in this target organ. Interest in the investigation of liver toxicity and injury in fishes stems from several motivations, including developing an understanding of vertebrate comparative physiology and anatomy; addressing problems in aquaculture associated with liver pathologic conditions caused by nutrition-related factors or improper storage of dietary components; analysis of the pathogenesis of liver neoplasia in selected fish species; and, more recently, development of biomarkers of exposure and effect and use of toxic alterations/responses in risk effects assessment. The latter interest stems from the fact that the aquatic medium is a sink for many anthropogenic contaminants (Long and Buchman, 1990; Mackay, 1992a, b; Tanabe et al., 2004). Pioneering workers recognized the unique strengths emanating from toxicological and biomedical studies comparing the spectrum of vertebrates (Guarino, 1987). Also, within the taxonomic class of fishes, where the largest group of vertebrates are found, comparative approaches can provide important insights, given the numerical, physiological, and ecological diversity herein. Recently, the transfer and incorporation of exciting new molecular technologic advances from the biomedical arena to environmental monitoring and assessment have been realized (Larkin et al., 2003; Rise et al., 2004; Williams et al., 2003). Strengths of fish models are now increasingly recognized and being used by the biomedical community (Barut, 2000; Dodd et al., 2000; Larkin et al., 2003; Loosli et al., 2000). Students of fish liver toxicology will need to achieve integration of various approaches/disciplines to use these new tools effectively and to interpret findings in their model systems. There is a need to push our understanding of fish liver toxicology while maintaining contact with advances in the biomedical arena. We feel that the time is ripe for a critical assessment of the hepatic toxicology of fishes, and we hope that this chapter portrays the progress achieved and stimulates and guides future studies.