Purucker E, Marschall H U, Winograd R, Matern S
Department of Internal Medicine III, Medical Faculty, Aachen University of Technology, Germany.
Biochim Biophys Acta. 2001 Apr 3;1526(1):44-52. doi: 10.1016/s0304-4165(01)00096-4.
Isoursodeoxycholic acid (isoUDCA), the 3 beta-epimer of ursodeoxycholic acid (UDCA), may have pharmaceutical potential because of its similar hydrophilicity and in vitro cytoprotection as compared with UDCA. We compared metabolism and effects on cholestasis of UDCA and isoUDCA in experimental cholestasis in rats. Cholestasis was induced by bile duct ligation. For bile flow and biliary bile acid analysis, UDCA or isoUDCA were infused intraduodenally. For the study of chronic effects, chow was supplemented with 2.5 g/kg UDCA or isoUDCA for 3 weeks. Sham-operated animals served as controls. IsoUDCA became completely converted to UDCA in the liver. Choleresis and biliary bile acids were the same after the intraduodenal administration of either compound. Oral administration of UDCA or isoUDCA significantly improved liver biochemistry but not clinical and histological parameters in chronic cholestasis. The decrease of serum cholic acid in control animals was more pronounced after isoUDCA (-93%) than after UDCA (-76%). Only after UDCA, this decrease was compensated by increases of UDCA, beta-muricholic acid (MCA), and Delta(22)-beta-MCA. Our results show that isoUDCA has the same effect on choleresis and liver biochemistry as UDCA. IsoUDCA features pro-drug characteristics of UDCA and causes compared to the latter lower serum bile acid concentrations in non-cholestatic animals.
异去氧胆酸（isoUDCA）是熊去氧胆酸（UDCA）的3β-差向异构体，因其与UDCA具有相似的亲水性和体外细胞保护作用而可能具有药学潜力。我们比较了UDCA和isoUDCA在大鼠实验性胆汁淤积中的代谢情况及其对胆汁淤积的影响。通过胆管结扎诱导胆汁淤积。为了进行胆汁流量和胆汁胆汁酸分析，将UDCA或isoUDCA经十二指肠注入。为了研究慢性影响，在大鼠饲料中添加2.5 g/kg UDCA或isoUDCA，持续3周。假手术动物作为对照。IsoUDCA在肝脏中完全转化为UDCA。十二指肠内给予任何一种化合物后，胆汁分泌和胆汁胆汁酸情况相同。口服UDCA或isoUDCA可显著改善慢性胆汁淤积时的肝脏生化指标，但对临床和组织学参数无改善作用。与UDCA（-76%）相比，isoUDCA使对照动物血清胆酸的降低更为明显（-93%）。仅在给予UDCA后，这种降低被UDCA、β-鼠胆酸（MCA）和Δ(22)-β-MCA的增加所补偿。我们的结果表明，isoUDCA对胆汁分泌和肝脏生化指标的影响与UDCA相同。IsoUDCA具有UDCA的前药特性，与后者相比，在非胆汁淤积动物中可导致更低的血清胆汁酸浓度。
