title: The toxic effects and fate of intravenously administered zearalenone in goats.
abstract: To clarify the toxic effects and fate of zearalenone (ZEA) in ruminants, we studied histopathological changes and toxicokinetic profiles in goats administered with a single intravenous (iv) injection of ZEA at doses of 2.4 mg/kg bw and 1.2 mg/kg bw, respectively. The expression of the mRNA of estrogen receptor (ER) alpha and beta in tissues was also investigated. The histopathological study revealed that ZEA caused hepatocellular swelling and lymphocytic infiltration in the liver, kidney, and uterus. The expression of ERalpha mRNA was enhanced by ZEA in association with the histopathological changes, indicating the possible involvement of ERalpha in the toxic effects of ZEA. For toxicokinetic profiles, blood plasma, urine, and feces were collected consecutively after iv injection of ZEA and analyzed for ZEA and its metabolites with high performance liquid chromatography (HPLC). alpha-Zearalenol (ZOL) and beta-ZOL were detected with ZEA, but alpha-zearalanol (ZAL), beta-ZAL, and zearalanone were below the detection limits. The distribution half-life (t(1/2alpha)) and elimination half-life (t(1/2beta)) of ZEA were 3.15 and 28.58h, respectively. ZEA, alpha-ZOL, and beta-ZOL were excreted in urine and feces, with beta-ZOL being the predominant metabolite. The ZEA and ZOL in urine were largely in their glucuronide and/or sulphate conjugated forms, while those in feces were largely in their free forms. This study showed the toxic effect of zearalenone and its metabolites, and their pharmacokinetic characteristics in goats.
authors.affiliation: Laboratory of Veterinary Public Health, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Dong
authors.forename: X J
authors.initials: XJ
authors.lastname: He
authors.forename: P
authors.initials: P
authors.lastname: Tulayakul
authors.forename: J-Y
authors.initials: JY
authors.lastname: Li
authors.forename: K-S
authors.initials: KS
authors.lastname: Dong
authors.forename: N
authors.initials: N
authors.lastname: Manabe
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.forename: S
authors.initials: S
authors.lastname: Kumagai
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics; D047629:Estrogen Receptor beta / Q000096:biosynthesis / Q000235:genetics; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006041:Goats; D006207:Half-Life; D006868:Hydrolysis; D007275:Injections, Intravenous; D008099:Liver / Q000473:pathology; D008297:Male; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D016610:Tissue Embedding; D015025:Zearalenone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal; D012333:RNA, Messenger; D015025:Zearalenone; D012313:RNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases