Page 348 - The Toxicology of Fishes

328 The Toxicology of Fishes

Metabolism as Factor in Liver Toxicity ................................................................................................368
Responses of Fish Liver to Reference Hepatotoxicants .......................................................................370
Summary of Acetaminophen Review ..........................................................................................370
Summary of Allyl Formate Review.............................................................................................370
Summary of Carbon Tetrachloride Review................................................................................370
Hepatocytes Under Toxic Exposure ......................................................................................................372
Lipopigments................................................................................................................................372
Lysosomes ....................................................................................................................................372
Peroxisomes..................................................................................................................................373
Rough and Smooth Endoplasmic Reticulum...............................................................................373
Nucleus and Mitochondria...........................................................................................................374
Liver Alterations in Fish Exposed to Environmental Pollutants ..........................................................374
Linkage of Biological Responses to Environmental Pollutants in Water and Sediment ..................... 376
Need for Future Research......................................................................................................................378
References..............................................................................................................................................379

Introduction

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 occupa-
tional 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 verte-
brates (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.

The Liver as a Target Organ
In part, the structure and function of the normal liver in fishes make it a target organ for toxic chemicals.
To better understand this statement, we must first consider the position of the liver, its afferent and
efferent vascular relationships, its microvascular properties that facilitate uptake, and how toxicants