Effect of ascorbic acid on the intestinal absorption of bile salts and metabolism of cholesterol in guinea pigs.

Abstract

Effect of ascorbic acid on in situ small intestinal absorption and hepato-biliary system of bile salts was investigated, by employing guinea pigs, for the purpose of explaining the physiological role of it to lower serum cholesterol. Firstly, the major bile acid and its salt were identified as chenodeoxycholic acid and its taurine conjugate, respectively. The critical micelle concentration (cmc) value of sodium chenodeoxycholate was estimated to beabout 0.9 mM, suggesting approximately the same order as reported on others with di-hydroxy groups. Added ascorbic acid did not exert any effect on the cmc value. Sodium taurochenodeoxycholate was favorably absorbed from the ileum portion of guinea pigs, and the absorption there appeared to obey such a type of saturation kinetics as has been demonstrated with other bile salts. Ascorbic acid was observed to inhibit the absorption significantly and especially in the lower concentration region of sodium taurochenodeoxycholatethan its cmc, where the percentage of inhibition was approximately 30 to 35. Double reciprocal treatment did not indicate any feasibility of competitive inhibition for the system of taurochenodeoxycholate and ascorbic acid. This effect of ascorbic acid should be explained neither by a change in physicochemical properties of the bile salt nor the direct action on intestinal mucosa, based on the results of cmc and additional pretreatment tests, but may be rather discussed by some participation in the hydrolysis and/or dehydroxylation of that salt occurring in the intestinal tissues other than mucosal membrane. Intraperitoneal administration of this vitamin and its dehydro form for 4 days enhanced the biliary amount of total chenodeoxycholate by about 60% of the control. Both in situ and in vitro experiments supported the in vivo results, so this metabolic aspect could be also recognized as one of the physiological functions of ascorbic acid which has been reported to lower serum cholesterol, in addition to suppressive effect on the ileal absorption of taurochenodeoxycholate.