Effects of Dietary Di(2-ethylhexyl)phthalate on the Metabolism of Tryptophan to Niacin in Mice

Abstract

Abstract:We have reported the effect of di(2-ethylhexyl)phthalate (DEHP) on the tryptophan (Trp)-niacin pathway in rats. To clarify the universal effect of DEHP on rodents, we studied whether DEHP also has an effect on Trp metabolism in mice. Mice were fed a niacin-free, 20% casein diet supplemented with DEHP for 21 days. Feeding with DEHP decreased the body weight gain and increased the liver weight in correlation with the dose level of DEHP. The administration of DEHP significantly increased the formation of quinolinic acid and the lower metabolites of the Trp-niacin pathway. The flux of niacin in the lower part of the Trp-niacin pathway in mice was enhanced by feeding with DEHP. Key words: niacin, phthalate esters, tryptophan lower metabolites were increased by feeding rats a diet containing DEHP [4]. However, there are no reports on the effect of DEHP on Trp to niacin metabolism in the mouse. To further clarify the universal effect of DEHP on rodents, we investigated whether DEHP also has an effect on Trp metabolism in mice.Vitamin-free milk casein, sucrose, L-methionine, nicotinamide (Nam), and anthranilic acid (AnA) were purchased from Wako Pure Chemical Industries (Osaka Japan). Kynurenine sulfate, kynurenic acid (KA), 3-hydroxyanthranilic acid (3-HA), and N 1 -methylnicotinamide (MNA) chloride were purchased from Tokyo Kasei Kogyo (Tokyo, Japan). Phthalic acid esters (PhEs), which are known to cause tetany of fish, and malformation of the mouse fetus, are used in a variety of industrial applications and they are constituents of diverse products such as paints, adhesives, cosmetics and polyvinylchloride plastics [10]. These esters are widely distributed throughout the environment and also have been detected in animals and humans [12,23]. Short-term administration of di(2-ethylhexyl)phthalate (DEHP) to rats causes liver enlargement with a marked proliferation of peroxisomes [6,7,9]. To clarify the mechanism of toxicity of PhEs in rats, we have already investigated the administration of PhEs such as DBP [21] and DEHP [3] which disturbed the metabolism of de novo NAD biosynthesis. The formation of the key metabolite of tryptophan (Trp) to the niacin pathway, quinolinic acid (QA), and its

The Formation of Nicotinamide by Administration of Di(2-ethylhexyl)phthalate Does Not Cause Growth Retardation in Young Rats in Contrast with Excess Exogenous Administration of Nicotinamide

“…We found and have reported that mono(ethylhexyl)phthalate (MEHP), a metabolite of DEHP, inhibits the enzyme activity of ACMSD, and increases the formation of QA, causing it to increase further metabolites such as Nam. [7][8][9][10][11][12] Phthalic acid does not accumulate in the liver, so the reaction of QPRT might not be inhibited.…”

“…These esters have been detected in animals and humans. [2][3][4] We have reported that the administration of phthalic acid esters such as dibutylphtahlate 5,6) and DEHP [7][8][9][10][11][12] disturbed the metabolism of de novo NAD biosynthesis. Concretely, the administration of phthalic acid esters increased the formation of QA (a key intermediate of the de novo NAD biosynthesis) and its metabolites.…”

Comparison of the Effects of Di(2-ethylhexyl)phthalate, a Peroxisome Proliferator, on the Vitamin Metabolism Involved in the Energy Formation in Rats Fed with a Casein or Gluten Diet

“…2,3) These esters are widely distributed throughout the environment and have been detected in animals and humans. 4) We have already reported that the administration of phthalic acid the esters such as di-n-butylphthalate 5) and di(2-ethylhexyl)phthalate (DEHP) [6][7][8][9][10] disturbed the de novo nicotinamide (Nam) synthesis from tryptophan (Trp).…”