J. Lipid Res.
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Journal of Lipid Research, Vol. 9, 244-253, March 1968
Copyright © 1968 by Lipid Research, Inc.

Experimental cholelithiasis in the rabbit induced by cholestanol feeding: effect of neomycin treatment on bile composition and gallstone formation

Alan F. Hofmann , Victor Bokkenheuser , Robert L. Hirsch , and Erwin H. Mosbach

The Rockefeller University, the Public Health Research Institute of the City of New York, Inc., and the Bureau of Laboratories, New York City Department of Health, New York 10009

Fed cholestanol is converted by the rabbit to 5agr-bile acids which coprecipitate with the normally occurring 5ßbeta;-bile acids to form gallstones composed of calcium and sodium glycoallodeoxycholate and glycodeoxycholate. The present study shows that oral administration of large doses of neomycin prevents gallstone formation in the cholestanol-fed rabbit and reduces the elevated concentration of allodeoxycholic acid in bile, with a reciprocal increase in allocholic acid concentration. The reduction in the concentration of allodeoxycholic acid and in the incidence of gallstones is proportional to the dose of neomycin; at a concentration of allodeoxycholic acid below about 20% of total bile acids, gallstone formation does not occur. Neomycin probably exerts its action by modifying the anerobic intestinal flora which dehydroxylate allocholic acid to allodeoxycholic acid; if so, this suggests that both hepatic and bacterial transformations are essential steps in the pathogenesis of cholestanol-induced cholelithiasis.

The bile of rabbits on a normal diet contains allodeoxycholic acid (5% of total bile acids). A similar decrease in allodeoxycholic acid concentration and reciprocal increase in allocholic acid concentration is observed when neomycin is administered to rabbits on a normal diet.

Supplementary key words 5agr-cholestan-3ßbeta;-ol metabolism • rabbit • 3agr,12agr-dihydroxy-5agr-cholanoic acid • 3agr,7agr,12agr-dihydroxy-5agr-cholanoic acid • experimental cholelithiasis • gallstones • 7agr-dehydroxylation • bile composition • bile acids • in vivo • intestinal microorganisms • neomycin

Submitted on October 4, 1967
Accepted on December 4, 1967


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