Awruch J, Mora M E, Lemberg A, Coll C T, Frydman R B
Programa de Investigaciones Bioorgánicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Biol Chem Hoppe Seyler. 1994 Sep;375(9):617-22. doi: 10.1515/bchm3.1994.375.9.617.
The effect of the administration of cobaltous chloride on the degradation of heme IX was investigated using perfusions of isolated rat livers. The presence of biliverdin IX beta (2%) in the bile fluid of cobaltous chloride treated rats support the hypothesis of the presence of a chemical oxidation of heme IX induced by the cobalt salt. In control rats the absence of biliverdin IX beta in the bile fluid was observed. When biliverdin IX beta was added to the perfusate it was excreted in the bile fluid as bilirubin IX beta without conjugation. An increase from approximately twofold to three-fold of the total bilirubins in the bile fluids of cobaltous chloride pretreated rats in relation with control rats was observed due to heme oxygenase enhanced activity. Bilirubin IX alpha diconjugates increased ca. 15% in the bile fluids of cobaltous chloride pretreated rats, after the addition of hemin IX. The increase could reflect the presence of a new molecular form of UDP-glucuronosyltransferase, which favours the formation of bilirubin IX alpha diglucuronide and therefore its preferential excretion into the bile. In the bile fluid of the rats pretreated with cobaltous chloride, other diconjugates of bilirubin IX alpha were also detected 120 min after the addition of hemin IX to the perfusate, consisting of glucose and glucuronate (5%) and xylose and glucuronate (5%).
使用离体大鼠肝脏灌注法研究了氯化钴给药对血红素IX降解的影响。在氯化钴处理的大鼠胆汁中存在胆绿素IXβ(2%),这支持了钴盐诱导血红素IX发生化学氧化的假说。在对照大鼠的胆汁中未观察到胆绿素IXβ。当将胆绿素IXβ添加到灌注液中时,它以未结合的胆红素IXβ形式排泄到胆汁中。由于血红素加氧酶活性增强,观察到氯化钴预处理大鼠胆汁中的总胆红素相对于对照大鼠增加了约两倍至三倍。在添加血红素IX后,氯化钴预处理大鼠胆汁中的胆红素IXα双结合物增加了约15%。这种增加可能反映了一种新的UDP-葡萄糖醛酸基转移酶分子形式的存在,它有利于胆红素IXα二葡萄糖醛酸酯的形成,因此其优先排泄到胆汁中。在向灌注液中添加血红素IX 120分钟后,在氯化钴预处理大鼠的胆汁中还检测到了胆红素IXα的其他双结合物,由葡萄糖和葡萄糖醛酸(5%)以及木糖和葡萄糖醛酸(5%)组成。