Taurine conjugate of ursodeoxycholate plays a major role in the hepatoprotective effect against cholestasis induced by taurochenodeoxycholate in rats

Abstract

Rats which were taurine-deprived through beta-alanine administration and untreated rats were used to elucidate the mechanism of hepatoprotective effects of ursodeoxycholate (UDC). Animals were infused with taurochenodeoxycholate (TCDC, 0.4 mumol.min-1.100 g-1) alone or in combination with tauroursodeoxycholate (TUDC), or with UDC (both 0.6 mumol.min-1.100 g-1) for 2 h. Ursodeoxycholate as well as TUDC prevented severe cholestasis and liver damage induced by TCDC infusion in both untreated and taurine-deprived rat groups. In untreated rats, however, UDC was less effective in hepatoprotection than TUDC as indicated by sequential changes in biliary LDH output during the period of 30 to 120 min (P < 0.05). In rats receiving UDC and TCDC, total biliary output of LDH for 2 h was significantly higher in taurine-deprived rats than that in the control (73.40 +/- 10.10 vs 41.14 +/- 12.56: P < 0.05), suggesting that the difference became greater upon taurine deprivation. In contrast, in rats receiving TUDC and TCDC, the protective effect was comparable for the taurine-deprived and untreated rats. When the animals were infused with UDC and TCDC, taurine-deprived rats exhibited a biliary excretion rate for TUDC half that of control rats (P < 0.05). Furthermore, a highly significant correlation was observed between the biliary excretion rate of TUDC and biliary output of LDH (r = -0.886, P < 0.0001). These results suggest that UDC conjugates, especially TUDC, and not UDC may play a major role in the prevention of cholestasis and liver cell damage caused by TCDC infusion.