The lymphatic absorption of dihydrolanosterol and cholesterol in the rat

Dihydrolanosterol (DHL) and its analogs have been studied extensively as ch olesterol biosynthesis inhibitors. They inhibit specific steps in cholester ol synthesis by inhibiting lanosterol demethylase and by suppressing HMG-Co A reductase. The present study was designed to estimate the lymphatic absor ption of DHL. For comparison, a cholesterol group was included. The left th oracic duct of male Wistar rats weighing between 210 and 230 g was cannulat ed. A lipid emulsion containing 0.75 mu Ci of either [H-3]-DHL or [H-3]-cho lesterol was given intragastrically. After the lipid meal, lymph was collec ted at 3 h intervals up to 9 h and then at 24 h. Radioactivity of DHL and c holesterol in the lymph was estimated. Lipid extracts of lymph specimens we re also subjected to thin layer chromatography and fractions of DHL, choles terol and their esters were isolated and the masses were estimated. There w ere no differences in lymph volumes between the two groups. However, absorp tion and esterification of DHL in lymph were significantly reduced compared with the cholesterol group. The marked decrease in the esterification of D HL is likely due to its poor absorption into the mucosal cell and subsequen tly into the lymphatic system. The amount of DHL available in the mucosal c ell for esterification may be a limiting factor.