In order to cast light on the anti-cholestatic and cytoprotective properties of
ursodeoxycholic acid (UDCA), intrahepatic transport and secretion of
bile salts and biliary
phospholipids were investigated by using isolated perfused livers from
colchicine-pretreated rats. Administration of
taurocholic acid (TCA) after
colchicine pretreatment induced marked
cholestasis.
Tauroursodeoxycholic acid (
TUDCA) treatment, in contrast, was associated with maintenance of bile flow, with excretion rates of
bile acids and
phospholipids similar to those in control animals. Furthermore, TCA-induced
cholestasis in
colchicine-treated rat livers was clearly decreased by co-administration of
TUDCA. Although simultaneous addition of UDCA also showed slight improvement, with or without
taurine pre-treatment, biliary
bile-salt analysis also showed that
cholestasis was markedly remitted as the excretion of
taurine-conjugated UDCA was increased. The results suggest that the cytoprotective and anti-cholestatic effects of
TUDCA may be linked to action at the intrahepatocyte level, represented by mild
detergent effects on organelle
lipids and preservation of intracellular transport even under microtubule-dysfunctional conditions. In addition, it was indicated that cytoprotective effects of UDCA may also be exerted after its conjugation with
taurine inside hepatocytes.