Effect of tritoqualine (TRQ) on bile secretion in rats

Abstract

An accelerating effect by TRQ-consecutive administration perorally on bile secretion in rats was investigated in comparison with phenobarbital (PB)-administered rats. The bile secretion velocity was increased significantly by administration of TRQ (25, 50, 100 mg/kg/day) or PB (50 mg/kg/day) compared to the control group. A 24% increase in the ratio of the liver weight to body weight was observed in the PB-administered group, but in the TRQ-administered group, a slight increase (5%) was seen compared with the control group. The concentration of excreted bile acid in the bile of rats to which TRQ and PB were administered were lower than that of the control group. However, when excreted bile acid content was represented in terms of wet liver weight, no difference was seen in the TRQ-administered group, but a 17% decrease was observed in the PB-administered group compared with the control group; and also, almost the same results were obtained with regards to the cholesterol and phospholipid in the bile. Though there was no difference of Na+, K+, or Cl- concentration in bile between the TRQ or PB-administered group and the control group, more Na+, K+ or Cl-/g wet liver was excreted in TRQ-treated group than the PB-administered group. TRQ was excreted through the bile duct promptly after an i.v. injection without an increase in the bile secretion, suggesting that the excretion of TRQ and its metabolites were not accompanied by the increase in bile secretion. These results indicate that the accelerating effect of TRQ on bile secretion was presumably derived from bile acid non-dependent bile secretion such as PB; however, a different pharmacological mechanism between TRQ and PB was presumed from the discrepancy of the decomposition in the secreted bile and of drug-metabolizing enzyme induction. Thus, it was suggested that there was a possibility that the accelerating action of bile secretion by TRQ was attributed to the activating effect of TRQ on the hepatocytes.