Identification of a toxic mechanism of the plasticizers, phtahlic acid esters, which are putative endocrine disrupters: time-dependent increase in quinolinic acid and its metabolites in rats fed di(2-ethylhexyl)phthalate.
We have reported that the administration of di(2-ethylhexyl)phthalate (DEHP) increased the formations of quinolinic acid (QA) and its lower metabolites on the tryptophan-niacin pathway. To discover the mechanism involved in disruption of the tryptophan-niacin pathway by DEHP, we assessed the daily urinary excretion of QA and its lower metabolites, and enzyme activities on the tryptophan-niacin pathway. Rats were fed with a niacin-free, 20% casein diet or the same diet supplemented with 0.1% DEHP or 0.043% phthalic acid and 0.067% 2-ethylhexanol added for 21 days. Feeding of DEHP increased the urinary excretions of QA and its lower metabolites in a time-dependent manner, and the increase of these excretions reached a peak at 11 days, but feeding of phthalic acid and 2-ethylhexanol had no effect. Feeding of DEHP, however, did not affect any enzyme activity including alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), affecting the formation of QA, on the tryptophan-niacin pathway.
Fukuwatari
Tsutomu
T
Laboratory of Food Science and Nutrition, Department of Life Style Studies, School of Human Cultures, The University of Shiga Prefecture, Hikone, Shiga 522-8533, Japan. fukkie@shc.usp.ac.jp
Suzuki
Yuko
Y
Sugimoto
Etsuro
E
Shibata
Katsumi
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002262:Carboxy-Lyases / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity*; D005247:Feeding Behavior / Q000187:drug effects; D000441:Hexanols / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009525:Niacin / Q000378:metabolism; D017378:Quinolinic Acid / Q000378:metabolism* / Q000652:urine; D051381:Rats; D014364:Tryptophan / Q000378:metabolism
D000441:Hexanols; D009525:Niacin; D014364:Tryptophan; D004051:Diethylhexyl Phthalate; D002262:Carboxy-Lyases; C024396:aminocarboxymuconate-semialdehyde decarboxylase; D017378:Quinolinic Acid; C034017:2-ethylhexanol