Metabolism and effects on biliary lipid secretion of murocholic acid in the hamster

Abstract

The metabolism of murocholic acid (MC), a 6β-hydroxylated bile acid, was investigated after intravenous (i.v.), intraduodenal (i.d.) or intragastric (i.g.) administration to bile fistula hamsters. The effects on biliary cholesterol and phospholipid secretion were measured during intravenous infusions of increasing doses of [ 3H]MC. At an infusion rate of 0.1 or 1 μmol · min −1· kg −1, the hepatic uptake was effective. More than 90% of the dose was recovered in bile within 4 h. A bolus injection of 500 μg of [ 3H]MC in the duodenum led to a rapid and efficient biliary secretion of radioactivity. Increasing i.v. infused doses of MC had no effect on bile flow or biliary cholesterol output compared to the controls. Phospholipid secretion was significantly reduced (0.113 μmol · min −1 · kg −1 versus 0.238 μmol · min −1 · kg −1 in controls per μmol · min −1 · kg −1 of excreted bile acids) as MC progressively replaced the endogenous bile acid pool in bile. After i.v. and i.d. administration, MC was secreted in bile as glyco and tauro conjugates without additional hepatic hydroxylation, sulfation or glucuronidation. The i.g. ingestion of MC followed by the faecal analysis of metabolites showed the formation of hyodeoxycholic acid and 3α-OH-6-oxo-5β-cholan-24-oic acid. An equivalent experiment with hyodeoxycholic acid gave MC and the same oxo bile acid. We concluded that MC is metabolized by the hamster liver as an endogenous bile acid, which undergoes intestinal bacterial transformation into a 6-oxo derivative and is then reduced into hyodeoxycholic acid. This process is completely reversible. Progressive replacement of endogenous bile acids in bile by infused MC does not modify choleresis and biliary cholesterol output. In contrast, the phospholipid secretion is decreased. This effect is probably related to the hydrophilic properties of MC.