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The toxic effects and fate of intravenously administered zearalenone in goats
Authors:M Dong  XJ He  P Tulayakul  J-Y Li  K-S Dong  N Manabe  H Nakayama  S Kumagai
Institution:1. 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;2. Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan;3. Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan;4. Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan;5. Department of Veterinary Public Health and Diagnostic Services, Faculty of Veterinary Medicine, Kasetsart University, Kamphaengsaen Campus, Nakorn-Pathom 73140, Thailand
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) α and β 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 ERα mRNA was enhanced by ZEA in association with the histopathological changes, indicating the possible involvement of ERα 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). α-Zearalenol (ZOL) and β-ZOL were detected with ZEA, but α-zearalanol (ZAL), β-ZAL, and zearalanone were below the detection limits. The distribution half-life (t1/2α) and elimination half-life (t1/2β) of ZEA were 3.15 and 28.58 h, respectively. ZEA, α-ZOL, and β-ZOL were excreted in urine and feces, with β-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.
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