title: The urinary ratio of 3-hydroxykynurenine/3-hydroxyanthranilic acid is an index to predicting the adverse effects of D-tryptophan in rats.
abstract: The adverse effects of D-tryptophan and the possibility of it being a surrogate index for predicting adverse effects in rats were investigated. Male rats were fed one of several test diets (20% casein diets with 0% (control), 0.1%, 0.2%, 0.3%, 0.4%, and 0.5% D-tryptophan) for 21 d, and 24-h urine samples on the final day of the experiment were collected. Analyses of food intake and body-weight changes revealed adverse effects to be observed in the group fed the 0.3% D-tryptophan diet. We propose urinary levels of 3-hydroxykynurenine/3-hydroxyanthranilic acid to be surrogate indicators for predicting the adverse effects of D-tryptophan from the break point of body-weight gains and urinary levels of D-tryptophan metabolites. The reaction 3-hydroxykynurenine→3-hydroxyanthranilic acid is catalyzed by the pyridoxal phosphate-dependent enzyme kynureninase. Increasing urinary 3-hydrokykynurenine indicates kynureninase deficiency. Intake of D-tryptophan in rats fed the 0.3% D-tryptophan diet was 0.21 g/kg body weight and feeding of the 0.3% D-tryptophan diet did not elicit adverse effects. Thus, the safe level of D-tryptophan was less than 0.2% in the diet, 0.15 g/kg body weight, in rats.
authors.affiliation: Department of Nutrition, School of Human Cultures, University of Shiga Prefecture.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ohno
authors.forename: Mitsue
authors.initials: M
authors.lastname: Sano
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fukuwatari
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism*; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000209:etiology*; D000818:Animals; D004032:Diet; D006867:Hydrolases / Q000172:deficiency*; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D008297:Male; D017208:Rats, Wistar; D014364:Tryptophan / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics; D015430:Weight Gain / Q000187:drug effects
chemical_list: D015095:3-Hydroxyanthranilic Acid; C005045:3-hydroxykynurenine; D007737:Kynurenine; D014364:Tryptophan; D006867:Hydrolases; C021480:kynureninase