The lymphatic absorption of dihydrolanosterol and cholesterol in the rat.

ABSTRACT

Dihydrolanosterol (DHL) and its analogs have been studied extensively as cholesterol biosynthesis inhibitors. They inhibit specific steps in cholesterol synthesis by inhibiting lanosterol demethylase and by suppressing HMG-CoA reductase. The present study was designed to estimate the lymphatic absorption of DHL. For comparison, a cholesterol group was included. The left thoracic duct of male Wistar rats weighing between 210 and 230 g was cannulated. A lipid emulsion containing 0.75microCi of either [3H]-DHL or [3H]-cholesterol was given intragastrically. After the lipid meal, lymph was collected at 3 h intervals up to 9 h and then at 24 h. Radioactivity of DHL and cholesterol in the lymph was estimated. Lipid extracts of lymph specimens were also subjected to thin layer chromatography and fractions of DHL, cholesterol and their esters were isolated and the masses were estimated. There were no differences in lymph volumes between the two groups. However, absorption and esterification of DHL in lymph were significantly reduced compared with the cholesterol group. The marked decrease in the esterification of DHL is likely due to its poor absorption into the mucosal cell and subsequently into the lymphatic system. The amount of DHL available in the mucosal cell for esterification may be a limiting factor.