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.
Weekley
L B
LB
Kimbrough
T D
TD
Llewellyn
G C
GC
D000348:Aflatoxins / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001652:Bile Ducts / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004032:Diet; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007736:Kynurenic Acid / Q000652:urine; D007737:Kynurenine / Q000652:urine; D008099:Liver / Q000201:enzymology; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced; D051381:Rats; D012701:Serotonin / Q000032:analysis; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D000348:Aflatoxins; D012701:Serotonin; D007737:Kynurenine; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D007736:Kynurenic Acid