TAUROHYODEOXYCHOLIC ACID PROTECTS AGAINST TAUROCHENODEOXYCHOLIC ACID-INDUCED CHOLESTASIS IN THE RAT

The prevention of the hepatotoxic effects produced by intravenous infu sion of taurochenodeoxycholic acid (TCDCA) by coinfusion with taurohyo deoxycholic acid (THDCA) was evaluated in bile fistula rats; the hepat oprotective effects of the latter were also compared with those of tau roursodeoxycholic acid (TUDCA). Rats infused with TCDCA at a dose of 8 mu mol/min/kg showed reduced bile flow and calcium secretion, as well as increased biliary release of alkaline phosphatase (AP) and lactate dehydrogenase (LDH). This was associated with a very low biliary secr etion rate of TCDCA (approximate to 1 mu mol/min/kg). Simultaneous inf usion of THDCA or TUDCA at the same dose preserved bile flow and almos t totally abolished the pathological leakage of the two enzymes into b ile. The effect was slightly more potent for THDCA. The maximum secret ion rate of TCDCA increased to the highest value (8 mu mol/min/kg) whe n coinfused with either of the two hepatoprotective bile acids (BA), w hich were efficiently and completely secreted in the bile, without met abolism. Calcium output was also restored and phospholipid (PL) secret ion increased with respect to the control saline infusion. This increa se was higher in the THDCA study. These data show that THDCA is highly effective in the prevention of hepatotoxicity induced by intravenous infusion of TCDCA by facilitating its biliary secretion and reducing i ts hepatic residence time; this was associated with selective stimulat ion of PL biliary secretion.