Gallstones in the golden hamster. XXXVI. Pigment cholelithiasis produced by retinoic acid.

Abstract

Previously we have reported on the pigmentary lithogenic action of vitamin A in the form of retinol acetate. In the present work the possible lithogenic action of retinoic acid was tested, since this differs from retinol in several metabolic aspects, which can contribute to the understanding of the pathogenesis of the pigment cholelithiasis produced by vitamin A. Two experiments were performed in which the lithogenicity of retinol acetate added to a colony chow at the level of 25,000 IU%, was compared with that of 3 dietetic levels of all-trans retinoic acid. In the first experiment seric triglycerides were determined in order to establish whether there is a relation between the hypertriglyceridemic effect of retinoids and their lithogenicity; in the second experiment GPT and GOT were determined as indicators of hepatotoxicity. The results showed that the retinoic acid at levels of 24,000 and 35,000 IU% of diet, produced a cholelithiasis incidence similar to that of 25,000 IU% of retinol acetate, whereas the retinoic acid level of 12,000 IU% was not lithogenic. The dietetic retinoic acid produced a reduction of hepatic vitamin A, that was directly proportional to the level supplied. There was no relation between the hypertriglyceridemic effect of retinoids and its lithogenicity. The retinoids produced a light increase in GPT, which was higher with retinol acetate, whereas GOT had not significative changes. It is concluded that all-trans retinoic acid produces pigment gallstones in the hamster, with an incidence similar to that produced by retinol acetate.