Mesa V A, Fevery J, Heirwegh K P, De Groote J
Hepatology. 1985 Jul-Aug;5(4):600-6. doi: 10.1002/hep.1840050413.
Bilirubin seems to share the biliary excretion pathway with other organic anions, but not with bile acids. We studied the effects of the organic anion ioglycamide, an iodinated contrast agent, on bilirubin metabolism in Wistar rats. This compound does not undergo conjugation and is characterized by a maximal biliary secretory rate (Tm). The results show that in spite of producing a 3-fold increase in bile flow, ioglycamide excretion under Tm conditions decreased the output of unconjugated bilirubin and its monoconjugate by approximately 90%. Diconjugated bilirubin decreased by only 50% and became by far the predominant pigment in bile (86.5 +/- 6.0% of total pigment vs. 61.0 +/- 4.0% in basal conditions, n = 12). Unconjugated and monoconjugated bilirubins changed in parallel suggesting that the former arises from the monoconjugates. In serum, diconjugated bilirubin augmented from trace amounts to 1.15 +/- 0.17 mumole per liter. Total conjugated pigments in serum increased from 5 to 85% of total bilirubin. Bile acid output remained unchanged. Pretreatment of rats with ioglycamide altered neither the activity of bilirubin UDP-glucuronyltransferase nor the ratio of diconjugate to monoconjugate formed at both low (25 microM) and high (164 microM) bilirubin concentrations. The observed biological effects of ioglycamide were dose-dependent and fully reversible. We suggest that ioglycamide interferes with the excretion of conjugated bilirubins ("bilirubinostasis"). The monoconjugates retained in the hepatocyte might then undergo more efficient transformation to diconjugates, the latter thus becoming the most important bile pigments in serum and bile.
胆红素似乎与其他有机阴离子共用胆汁排泄途径，但与胆汁酸不同。我们研究了有机阴离子碘海醇（一种碘化造影剂）对Wistar大鼠胆红素代谢的影响。该化合物不会进行结合反应，其特点是具有最大胆汁分泌率（Tm）。结果表明，尽管碘海醇使胆汁流量增加了3倍，但在Tm条件下其排泄使未结合胆红素及其单结合物的输出量减少了约90%。双结合胆红素仅减少了50%，并成为胆汁中迄今为止的主要色素（占总色素的86.5±6.0%，而基础条件下为61.0±4.0%，n = 12）。未结合胆红素和单结合胆红素平行变化，表明前者由单结合物产生。在血清中，双结合胆红素从微量增加到每升1.15±0.17微摩尔。血清中总结合色素从总胆红素的5%增加到85%。胆汁酸输出量保持不变。用碘海醇预处理大鼠，在低（25微摩尔）和高（（164微摩尔）胆红素浓度下，既不改变胆红素UDP-葡萄糖醛酸基转移酶的活性，也不改变形成的双结合物与单结合物的比例。观察到的碘海醇生物学效应具有剂量依赖性且完全可逆。我们认为碘海醇干扰结合胆红素的排泄（“胆红素潴留”）。保留在肝细胞中的单结合物可能随后更有效地转化为双结合物，因此双结合物成为血清和胆汁中最重要的胆汁色素。
