Page 398 - The Toxicology of Fishes

378 The Toxicology of Fishes

of oil pollution on mussels and fish in the Ligurian Sea in Italy (Viarengo et al., 2001). Identification
of lipopigment per se is not difficult, but quantification of abundance and size may not be cost effective
for routine monitoring. Biochemical measurement of lipid peroxidation could be employed to indicate
formation of lipopigments in liver.
Lysosomal alterations in fish hepatocytes have been recommended as potential cytological biomarkers
for environmental pollutants. Köhler et al. (2002) demonstrated a good dose–response relationship
between the severity of lysosome alterations in liver of Platichthys flesus and the levels of xenobiotics
pollution. The results support the use of lysosomal membrane destabilization together with lysosomal
enlargement as a prognostic biomarker for toxicant-induced fish liver dysfunction in biomonitoring
programs (Broeg et al., 1999; Köhler et al., 2001, 2002). Methods used in the determination of lysosomal
integrity in fish hepatocytes have been well established (Köhler 1991, 1992; Lowe et al., 1992), but no
information is available on the reversibility of lysosomal changes upon withdrawal of contaminants. If
the induction is transient and reversible, this cytological damage is short term, and induction of the
cytological changes will signify recent exposure of the fish to pollutants. If the change is irreversible,
permanent damage is implicated. Such information is essential for interpreting field data and evaluating
the robustness of these cytological markers for pollution monitoring and risk assessment.
Both lysosomal stability and lipopigment content in fish liver have shown promise and may be useful
early warning signals to indicate exposure to and effects of persistent environmental pollutants, providing
that the effects of seasonal variations (temperature, salinity, and food availability) and reproductive status
(sex and maturity) have been studied and standardized for the test fish species. Such information is
urgently needed for evaluating the applicability of the two cytological biomarkers in pollution monitoring.
The fact that major attention in biomarker production and application has focused on the liver underscores
the importance of this target organ.

Need for Future Research

More data on responses of fish liver to hepatotoxicants are needed. We have a number of reports
describing toxic responses in fish liver, but usually only specific aspects are addressed, and rarely do
we have a database comparable to reference hepatotoxicants in mammals, where information regarding
the mechanisms, pathology, and toxicology is available. With fish, we usually have only bits, but no
complete picture. For rodent liver, we are aware of pathological liver changes typical for, for example,
oxidative stressors, and we can even cluster hepatotoxins on the basis of gene expression profiles, but
for fish we have no such systematic understanding. To broaden our database on this point requires
generating a database on the mechanisms and pathological and toxicological effects of chemicals that
act specifically on the liver (not just chemicals that may target another organ and have some side effects
on the liver as well), which is essential for developing our still very descriptive approach to fish liver
toxicology into one of sound and integrative science.
In addition to broadening our knowledge and understanding on toxic response patterns, both molecular
and histological ones, we have to know much more regarding the basic functional properties of fish
liver; for example, although the various sinusoidal and biliary transporters in rodent liver are well
characterized, we are just beginning these studies in fish. We have some evidence for an MDR1-like
transporter, and evidence is emerging for MRP-like transporters, but all this is still very fragmentary
information. As long as we lack sufficient understanding of the basic functional traits of fish liver, we
will not be able to understand and classify toxic effects.
We need to know much more regarding the relationships between the various liver cell types. Much
liver toxicity in mammals is not triggered from hepatocyte responses but through signaling between the
various liver cell types. Here, our knowledge on fish liver is almost nonexistent, despite the importance
of this aspect for liver toxicology. Currently, liver histopathology is used mainly as a descriptive tool to
assess the health status of fish exposed to toxicants. To more completely understand toxic responses in
the liver and to further apply this knowledge, we need to integrate molecular, biochemical, physiological,
and morphological findings from the cellular through organ level.