Page 100 - The Toxicology of Fishes

80 The Toxicology of Fishes

100
PERCENTAGE BOUND 60
80

40

20
0
0 2 4 6 8 10
mM SULFADIMETHOXINE

FIGURE 3.11 Plasma binding of sulfadimethoxine in rats (solid circles) and rainbow trout (solid squares) over a dosage
range of 0.2 to 10 mM.

1988). This type of binding appears to be relatively nonspecific and nonsaturable and may be dominated
by chemical interactions with lipid and lipoprotein. Similar relationships are obtained, however, when
chemicals are added to solutions containing bovine serum albumin or human serum albumin (Figure
3.12). Using blood serum from mosquitofish (Gambusia affinis), Denison and Yarbrough (1985) found
that the binding of lipophilic organochlorine insecticides increased with chemical polarity. Moreover,
pretreatment of serum with endrin or aldrin substantially reduced the amount of subsequent DDT binding.
Both of these observations are indicative of chemical binding to proteins.
Methylmercury in plasma binds reversibly to sulfur-containing molecules such as glutathione and the
amino acid cysteine. The cysteine-bound form is of particular interest to toxicologists because it is
transported by a neutral amino acid carrier system into sensitive tissues such as the brain (Kerper et al.,
1992). In rainbow trout, however, 90% of whole-blood methylmercury is bound to hemoglobin in red
blood cells (Giblin and Massaro, 1975). By limiting the amount of methylmercury available to interact
with plasma molecules, this binding to hemoglobin becomes an important determinant of methylmercury
kinetics and toxicity.
Heavy metals are transported in association with a variety of free proteins in plasma. Most of the
cadmium in the plasma of brown trout and humans is bound to albumin or an “albumin-like” protein.
Studies with carp, however, suggest that cadmium in plasma is primarily bound to a Mr 70,000 protein
identified as transferrin (De Smet et al., 2001). The very low levels of “albumin” in carp plasma may
account for this difference among species. Similarly, catfish serum proteins were shown to have much
higher affinity and binding capacity for zinc than the primary transport protein (albumin) identified in
other species (Bentley, 1991).

Tissue Affinity
Although chemical distribution at the beginning of an exposure is often determined by relative tissue
blood flows, many chemicals redistribute over time in accordance with their relative affinity for tissue
constituents. Lipophilic xenobiotics such as PCBs possess high affinity for tissues that have a high lipid
content. Distributional differences among species may therefore occur due to different patterns of lipid
deposition in organs and tissues; for example, Guiney and Peterson (1980) found that 60% of a dose of
2,2′,5,5′-tetrachlorobiphenyl in rainbow trout was contained in skeletal muscle and carcass, but in yellow
perch 70% was contained in viscera and carcass (excluding skeletal muscle). These patterns were
correlated with differences in the lipid content of each tissue, relative to that of other tissues. Similarly,
Zitko et al. (1974) found that differences in muscle lipid content of Atlantic herring (Clupea harengus)
and yellow perch correlated with differences in total PCB concentration.
Tissues that contain a large amount lipid may act as storage depots for lipophilic compounds. This
storage may protect against adverse effects by isolating a chemical away from its sites of toxic action.
Conversely, storage in these sites may prolong the overall residence time of a compound in the body
and promote accumulation during chronic exposures. By reducing adipose lipid stores, starvation may
result in a relatively rapid mobilization of accumulated chemical. When the rate of elimination from the