Itagaki Shirou, Sugawara Mitsuru, Kobayashi Michiya, Miyazaki Katsumi, Hirano Takeshi, Iseki Ken
Department of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University.
Drug Metab Pharmacokinet. 2004 Apr;19(2):150-4. doi: 10.2133/dmpk.19.150.
Long-Evans Cinnamon (LEC) rats have an abnormality similar to that observed in Wilson's disease in humans and are therefore a good animal model for the study of Wilson's disease. LEC rats develop hereditary hepatitis and severe jaundice. Mutant animals with hyperbilirubinemia have been widely used as animal models for human diseases. Among these mutant animals, Eisai hyperbilirubinemic rats (EHBR) have defective biliary excretion of organic anions. Thus, biliary excretion of sulfobromophthalein (BSP) and urinary excretion of phenolsulfonphthalein (PSP) in LEC rats were compared with those in Long-Evans Agouti (LEA) rats. In LEC rats, the excretion of BSP, a multidrug resistance-associated protein 2 (Mrp2/Abcc2) substrate, was significantly decreased compared to that in LEA rats. It has been reported that the transport function for organic anions on the kidney is maintained in EHBR. However, the urinary excretion of PSP is impaired in LEC rats. It is possible that organic anion transporters responsible for the urinary excretion of PSP in LEA rats and EHBR are impaired in LEC rats. It is important to elucidate the relationship between organic anion secretion and Wilson's disease.
长-伊文斯肉桂色（LEC）大鼠具有一种与人类威尔逊病中观察到的异常相似的情况，因此是研究威尔逊病的良好动物模型。LEC大鼠会发展出遗传性肝炎和严重黄疸。患有高胆红素血症的突变动物已被广泛用作人类疾病的动物模型。在这些突变动物中，卫材高胆红素血症大鼠（EHBR）的有机阴离子胆汁排泄存在缺陷。因此，将LEC大鼠中磺溴酞钠（BSP）的胆汁排泄和酚磺酞（PSP）的尿排泄与长-伊文斯刺鼠（LEA）大鼠进行了比较。在LEC大鼠中，作为多药耐药相关蛋白2（Mrp2/Abcc2）底物的BSP的排泄与LEA大鼠相比显著降低。据报道，EHBR中肾脏对有机阴离子的转运功能得以维持。然而，LEC大鼠中PSP的尿排泄受损。LEA大鼠和EHBR中负责PSP尿排泄的有机阴离子转运体在LEC大鼠中可能受损。阐明有机阴离子分泌与威尔逊病之间的关系很重要。
