Pigment cholelithiasis induced by vitamin A and its prevention by butylated hydroxytoluene

We previously reported on the induction by vitamin A of gallstones, rich in calcium and phosphate, in hamsters. On the other hand, it has been reported that the phenolic antioxidant butylated hydroxytoluene (BHT) potentiates the hepatotoxicity of vitamin A. In the present work we have tested the effect of BHT on the lithogenicity of vitamin A and on bile composition. The urinary excretion of calcium and phosphate was determined to assess a possible asymptomatic bone resorption due to vitamin A toxicity, and/or an effect of BHT on the homeostasis of calcium and phosphate. Three groups of 18 male hamsters were fed with the following diets for 70 days: Group 1, Purina Nutricubes (DB); Group 2, DB + 25,000 IU% retinol acetate (DL); Group 3, DL + 500 mg% BHT. Vitamin A (Group 2) induced gallstones in 78% of the animals, increased bile flow and biliary phosphate and calcium concentrations, and reduced those of bile salt, cholesterol and phospholipid. BHT (Group 3) reduced gallstone frequency to 5.5%, and decreased biliary phosphate, calcium and lipids toward more normal concentrations. Vitamin A alone or with BHT did not significantly affect food intake or urinary excretion of calcium and phosphate.