Disturbances in tryptophan metabolism in rats following chronic dietary aflatoxin treatment

Male Holtzman rats were fed 7.8 ppm mixed aflatoxins (AFT) for a 21-week period. At sacrifice there was extensive bile ductule cell proliferation and numerous precancerous changes evident in AFT-treated animals. The in vitro activity of hepatic holo-enzyme tryptophan 2, 3-dioxygenase was reduced in AFT-treated animals which correlated with a reduced urinary excretion of both kynurenine and kynurenic acid suggesting that this reduced tryptophan 2, 3-dioxygenase observed in vitro may be relevant to the in vivo response. The levels of serotonin and 5-hydroxyindole-3-acetic acid were found to be reduced in the pineal, pituitary, various brain regions and in duodenum of AFT-treated rats. It is proposed that the decreased levels of serotonin and 5-hydroxyindole-3-acetic acid in all tissues may be due to either a decreased free tryptophan pool or alterations in 5-hydroxyindole biosynthesis.