Page 104 - The Toxicology of Fishes

84 The Toxicology of Fishes

Sinusoidal Membrane
Mrp

Mrp
Hepatocytes

Pgp
Oatp
Canalicular Membrane

Small Bile Duct

Large Bile Duct

FIGURE 3.14 Hepatic tubule of the fish liver showing the origins of the biliary system and locations of xenobiotic
transporters. Efflux transporter isoforms of the multidrug resistance-associated protein family (Mrp) are located on both
the sinusoidal and canalicular membranes. P-glycoprotein (Pgp) is localized to the canalicular membrane, and isoforms of
the organic anion transporter polypeptide family (Oatp) are located on the sinusoidal membrane.

A variety of structural arrangements have been described for the liver and biliary tree of fish. In
general, fish do not possess the lobular structure and zonally oriented portal tracts observed in mammalian
livers (Eurell and Haensly, 1982; Hampton et al., 1989; Hinton and Couch, 1998; Robertson and Bradley,
1992; Schar et al., 1985). Instead, the hepatocytes are commonly arranged into tubular elements. In
rainbow trout, hepatocyte apices are directed toward the center of the tubule (Figure 3.14). At the center
of the tubule, plasma membranes of adjacent cells form bile canaliculi. Where a biliary space exists, the
biliary epithelial cells form junctional complexes with each other, and the hepatocytes on either side
form a wall of the biliary passageway. These biliary passageways lead in turn to the cholangioles, small
bile ducts, and large bile ducts. The contralateral or basal side of each hepatocyte faces a blood-filled
sinusoid surrounding the tubule. Individual tubules curve, branch, and anastomose to form a complex
network of parenchyma.
In salmon, multiple hepatic bile ducts empty into an elongated major duct that runs along the posterior
ventral margin of the liver. The cystic duct branches from the major bile duct and serves to divert bile
to the gallbladder. Bile originating from the major bile duct and gallbladder is collected in the common
bile duct and empties into the proximal intestine just posterior to the pyloric curvature of the stomach.
Some fish species, including members of the cod family, do not possess a gallbladder. It is thought that
for these species bile is secreted continuously into the intestine.
Studies with mammals have shown that the excretory function of the liver and bile is greatly facilitated
by the activity of specialized efflux transport proteins, including multidrug resistance-associated proteins
(Mrps) and P-glycoprotein (Pgp) (Ayrton and Morgan, 2001; Keppler and Konig, 2000; Yamazaki et al.,
1996). Mrps and Pgp belong to the highly conserved superfamily of ATP-binding cassette (ABC)
transporters, which have been identified in organisms ranging from yeast to humans. Both groups of