Abstract
Experiments were performed to assess chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) as to litholytic efficacy for biliary cholesterol gallstones, with the results as follows.
1. Groups of squirrel monkeys which had been maintained on a cholesterol-rich diet for twelve months were fed rations containing CDCA or UDCA over periods of 6 to 12 months, and compared to an untreated control group in respect of bladder bile composition, liver function and light and electron microscopic features of the liver tissue.
There was a conspicuous decrease in cholic acid (CA) content in bladder bile composition of CDCA-dosed animals as compared with animals given UDCA, and the bile from the CDCA-treated group showed a slightly higher content of lithocholic acid (LCA) whereas the UDCA-treated group virtually did not differ from the control group. Biochemical analysis of the liver function also revealed slightly abnormal values in the CDCA-treated group in which light microscopic evidence of modest cholestasis and pronounced electron opacities of hepatocytic mitochondria were observed. These findings seem to indicate that CDCA possesses a slightly greater hepatotoxic potential than UDCA in squirrel monkeys.
2. No significant differences were noted to exist in the composition of human bladder bile, drawn from the duodenum, among the three groups : cholesterol cholelithiasis, noncholesterol cholelithiasis and without cholelithiasis. It would follow that it is not always advisable to determine the indication for the use of litholytic medication solely on the basis of chemical analytic findings for the bile.
3. The effects of orally administrated CDCA and UDCA on the hepatic bile composition were investigated by way of collecting specimens via a T-tube from post-cholecystectomy patients. Both drugs caused decrease of cholesterol content in the percentage composition of hepatic bile whilst the lecithin content remaind essentially unchanged. The results may indicate that the decrease in biliary lithogenic index (L.I.) following administration of CDCA or UDCA is effected through the mechanism whereby the compounds suppress cholesterol excretion into the bile.
The data suggest the possibility that both CDCA and UDCA have litholytic activity for cholesterol stones, the efficacy being more conspicuous with UDCA as estimated from the findings in squirrel monkeys.
