β muricholic acid: a new hepatoprotective agent

Abstract

The hepatoprotective effect of β muricholate against cholestasis induced by hydrophobic steroids was studied in rats. Acute cholestasis was caused by intravenous infusion of taurochenodeoxycholate at 3 μmol/min/Kg for 3 hr in the bile fistula rats. Bile flow and bile salt secretion decreased gradually, whereas lactico dehydrogenase biliary leakage increased. Simultaneous infusion of β muricholate, at a rate of 1.5 μmol/min/Kg, ameliorated cholestasis induced by taurochenodeoxycholate, but an increase in lactico dehydrogenase persisted. Infusion of 4 μmol/min/Kg of β muricholate resulted in the quasi-complete biliary elimination of taurochenodeoxycholate and prevented the cholestatic and cytotoxic effects of taurochenodeoxycholate infusion alone. β muricholate was as effective as tauroursodeoxycholate. Moreover, severe chronic cholestasis induced by ethinyl estradiol was partially prevented by hydrophilic bile acid feeding. When β muricholate was given at a 50 mg/Kg/day dose, bile flow and bile salt secretion were increased. Both bile salt dependent and bile salt independent bile flow were significantly improved. Lastly, the hydrophilic-hydrophobic balance of β muricholate was estimated by surface tension measurements. β muricholate appeared to have a weak affinity for a hydrophobic interface. It generated a lower surface pressure than ursodeoxycholate and much more lower than chenodeoxycholate. The low surface activity of β muricholate could account for its non-toxicity and protective action towards hepatocyte membranes.