Page 393 - The Toxicology of Fishes

Liver Toxicity 373

(Bozzola and Russell, 1992; Holtzman, 1976). Alterations to lysosomal structure are usually associated
with a reduction in the stability of lysosomal membranes and an increase in lysosomal enzyme
activities, which may pose a potential risk to the health of the cell or the individual organism (Köhler,
1991; Moore, 1993). Reduced lysosome membrane stability and augmentation of lysosomes have
been reported in the livers of feral fish collected from highly contaminated waters, and in certain
cases, including exposure to heavy metals, increases in lysosome number were also observed (Baker,
1969; Braunbeck, 1998; Köhler, 1991; Köhler et al., 1992, 2002; Lanno et al., 1987; Lowe et al.,
1992; Segner and Braunbeck, 1990b; Woodworth et al., 1998). A recent study by Köhler and colleagues
(Köhler et al., 2002; Wahli, 2002) demonstrated a good dose–response relationship between the
severity of lysosomal alterations in livers of European flounder and the levels of xenobiotic pollution.
Moreover, increase in the size of lysosomes with accumulation of lipid and electron-dense content
(lipopigment) coincided with decreased lysosome membrane stability in fish livers (Köhler et al.,
2002). More prominent transitions of primary to tertiary lysosomes or lipopigments were observed
in the livers of Solea ovata and Epinephelus coioides subjected to BaP or PAH exposure. In general,
lysosome alterations are indicative of early cytopathological responses; they are sensitive but nonspe-
cific to a wide range of contaminants, including a diverse range of toxic metals and organic chemicals
(e.g., PAHs, PCBs, oil-derived hydrocarbons).

Peroxisomes
These single-membrane-limited organelles are ubiquitous in eukaryotic cells, where they play key roles
in major metabolic functions such as lipid metabolism (e.g., fatty acid β-oxidation) and cellular respi-
ration involving the metabolism of H O (e.g., production of oxidases and catalase) (Fahimi et al., 1983).
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Massive proliferation of peroxisomes may occur in animals after treatment with certain xenobiotics and
drugs (Fahimi and Cajaraville, 1995; Gibson and Lake, 1993; Moody, 1994). Peroxisome proliferation
is defined as an increase in either peroxisomal volume or numbers which may not always be accompanied
by an induction of peroxisomal enzymes (Reddy and Mannaerts, 1994). Catalase activity is one of the
marker enzymes used for assessing peroxisome proliferation biochemically (Moody, 1994). Channel
catfish (Ictalurus punctatus) and dab (Limanda limanda) exhibited an increase in catalase and superoxide
dismutase activity after exposure to PAH-contaminated sediments (Di Giulio et al., 1993; Livingstone
et al., 1993). Significant increases of volume density and absolute number of peroxisomes were dem-
onstrated in immature sole (Solea ovata) after intraperitoneal injection of fish with BaP (Au et al., 1999).
Induction of peroxisome proliferation has been reported in various animal tissues in response to PAHs
and other xenobiotics (Bentley et al., 1993; Fahimi and Cajaraville, 1995; Krishnakumar et al., 1995,
1997; Reddy et al., 1987). Inconsistent peroxisome reactions were found in the hepatocytes of rainbow
trout and zebrafish in response to various classes of toxicants; for example, the number of peroxisomes
was reduced in response to 4-chloroaniline and lindane, but proliferation occurred in response to 3,4-
dichloroaniline (Braunbeck, 1990; Braunbeck and Appelbaum, 1998). Species-specific variation and
toxicant specificity are the factors to be considered when studying the responses of peroxisome prolif-
eration in fish. It is also known that peroxisomal enzyme activity in fish could also be affected by other
biotic factors, such as sex, and abiotic factors, such as salinity, temperature, season, and feeding habit
(Braunbeck et al., 1987; Palace et al., 1993; Radi et al., 1987; Rocha et al., 1999).

Rough and Smooth Endoplasmic Reticulum
The hepatic cytochrome P450–monoxygenase system is a coupled electron transport system situated in
the endoplasmic reticulum of hepatocytes (Mansuy, 1998). Early proliferation of the hepatic ER system
was reported for fish exposed to PAHs, such as 3-methylcholanthrene (3-MC) and PCBs (Klaunig et al.,
1979; Schoor and Couch, 1979). BaP stimulated rough and smooth ER proliferation in the livers of
Solea ovata and Epinephelus coioides regardless of the route of exposure (water vs. intraperitoneal) (Au,
2004; Au and Wu, 2001; Au et al., 1999; Lemaire et al., 1992). A wide range of xenobiotics has been
shown to induce hepatic ER proliferation (Braunbeck, 1998). In general, fish hepatic ER induction is
nonspecific but sensitive to environmental contaminants.