Effect of tetrachlorodibenzo-p-dioxin (TCDD) on the glucuronidation of retinoic acid in the rat.

Effect of tetrachlorodibenzo-p-dioxin (TCDD) on the glucuronidation of retinoic acid in the rat.
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四氯二苯并-对-二恶英(TCDD)对大鼠视黄酸葡萄糖醛酸化的影响。

DOI:
10.1016/0304-4165(89)90134-7
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发表时间:
1989
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Zile,MH
Zile,MH
中科院分区:
--
文献类型:
--
作者:
Bank,PA;Salyers,KL;Zile,MH

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雄性大鼠单次口服四氯二苯并对二英(TCDD)10 μg/kg后,肝脏中的视黄酯减少了33%,但肾脏中的视黄酯增加了13倍,血清中的视黄醇增加了3倍。肝和肾微粒体尿苷二磷酸葡萄糖醛酸转移酶(UDPGT)对全反式视黄酸的活性增加3.7倍和2.6倍,分别为10天后,接触TCDD。通过与真实RG在反相高压液相色谱(HPLC)上共色谱法验证[3 H]视黄酰基β-葡萄糖醛酸苷(RG)的体外形成,鉴别视黄酸为β-葡萄糖醛酸酶处理后的水解产物,并通过负碎片质谱法、快速原子结合表征全反式视黄酰基葡萄糖醛酸苷。我们的结论是,增加视黄酸葡萄糖醛酸化可能是一个促成因素,肝脏消耗的维生素A和增加排泄的维生素A代谢产物后,TCDD曝光。
Administration of a single oral dose (10 μg/kg) of tetrachlorodibenzo-p-dioxin (TCDD) caused a 33% decrease in retinyl esters in the livers of male rats, but a 13-fold increase in retinyl esters in the kidney and a 3-fold increase in serum retinol. Liver and kidney microsomal uridine diphosphoglucuronosyltransferase (UDPGT) activity toward all-trans-retinoic acid was increased 3.7- and 2.6-fold, respectively, ten days following exposure to TCDD. Verification of the in vitro formation of [3H]retinoyl β-glucuronide (RG) was by cochromatography with authenic RG on reversed phase high pressure liquid chromatography (HPLC), identification of retinoic acid as the hydrolysis product after β-glucuronidase treatment, and the characterization of the all-trans-retinoyl glucuronide by negative fragment mass spectroscopy, fast atom bobardment. We conclude that increased retinoic acid glucuronidation may be a contributing factor to the hepatic depletion of vitamin A and the increased excretion of vitamin A metabolites following TCDD exposure.