title: Dioxin-Produced Alteration in the Profiles of Fecal and Urinary Metabolomes: A Change in Bile Acids and Its Relevance to Toxicity.
abstract: This study investigated dioxin-induced changes in metabolomes in pubertal rat excrement. The administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or restricting dietary intake (pair-fed group) markedly altered the metabolomic profile including lipids, hormones, and vitamins in the urine and feces. TCDD caused an increase in the fecal chenodeoxycholic acid and taurocholic acid content and in urinary adrenaline and 17β-estradiol, while the urinary melatonin level was reduced by TCDD. These changes were not observed in the pair-fed group. In accordance with the elevated level of fecal bile acids, TCDD reduced the intestinal expression of the apical sodium-dependent bile salt transporter, which plays a role in resorbing bile acids from the bile duct. In addition, CYP7A1, a rate-limiting enzyme for bile acid biosynthesis, was attenuated by TCDD treatment, although TCDD induced hepatic CYP8B1, an enzyme essential for cholic acid synthesis. Supplying cholic acid or chenodeoxycholic acid to TCDD-exposed rats tended to restore the TCDD-produced reduction in serum triglycerides, whereas no similar trend was observed in wasting syndrome and lipid accumulation in the liver. These results suggest that: 1) TCDD alters the circulating levels of bile acids and hormones via a mechanism distinct from an attenuation in dietary intake, although the majority of TCDD-induced changes in nutrient contents in the excrement is due to a reduction in food intake; and 2) TCDD facilitates the excretion of bile acids and disrupts their biosynthesis, resulting in the disturbance of lipid homeostasis.
authors.affiliation: Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University.
authors.forename: Saki
authors.initials: S
authors.lastname: Kakizuka
authors.forename: Tomoki
authors.initials: T
authors.lastname: Takeda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Komiya
authors.forename: Akihiko
authors.initials: A
authors.lastname: Koba
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.forename: Midori
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D031204:Caloric Restriction; D019363:Cytochrome P-450 CYP1A1; D004435:Eating / Q000187:drug effects; D005243:Feces / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D009929:Organ Size; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D017208:Rats, Wistar; D014556:Urine / Q000737:chemistry*
chemical_list: D001647:Bile Acids and Salts; D000072317:Polychlorinated Dibenzodioxins; D019363:Cytochrome P-450 CYP1A1