Prevention of Cholestanol-induced Cholelithiasis by Neomycin

Abstract

RABBITS receiving 0.25–1 per cent dietary cholestanol (5α-cholestan-3β-ol) for 3–6 weeks develop gall-stones which have been shown to consist predominantly of calcium, and sodium glycoallodeoxycholate (3α-, 12α-dihydroxy-5α-cholanoyl glycine)^1,2. Gall-stone formation in cholestanol-fed rabbits has been postulated to occur as follows: Cholestanol is absorbed from the intestinal tract of the rabbit and is transported to the liver where some of the stanol is metabolized to allocholic acid (3α-, 7α-, 12α-trihydroxy-5α-cholanoic acid). The latter is conjugated with glycine, excreted into the bile and eventually reaches the intestinal tract where it is hydrolysed and dehydroxylated by the intestinal bacterial flora to form allodeoxycholic acid (3α-, 12α-dihydroxy-5α-cholanoic acid). This dihydroxy bile acid is reabsorbed and returns to the liver where it is conjugated with glycine and re-excreted into the bile as glycoallodeoxycholate. The mixed calcium and sodium salt of the latter is relatively insoluble in bile², and therefore is thought to be the cause of gall-stones in cholestanol-fed rabbits. In contrast, the calcium–sodium salt of glycodeoxycholate is relatively soluble in aqueous media.