Comparison of the disposition behavior of organic anions in an animal model for Wilson's disease (Long-Evans Cinnamon rats) with that in normal Long-Evans Agouti rats.
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.
Itagaki
Shirou
S
Department of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University.
Sugawara
Mitsuru
M
Kobayashi
Michiya
M
Miyazaki
Katsumi
K
Hirano
Takeshi
T
Iseki
Ken
K
D000818:Animals; D000838:Anions / Q000378:metabolism*; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006527:Hepatolenticular Degeneration / Q000235:genetics / Q000378:metabolism*; D007202:Indicators and Reagents; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics; D051381:Rats; D020332:Rats, Inbred LEC; D020318:Rats, Long-Evans; D013056:Spectrophotometry, Ultraviolet; D013448:Sulfobromophthalein / Q000493:pharmacokinetics
C000715087:ABCC2 protein, human; D000838:Anions; D007202:Indicators and Reagents; D000089762:Multidrug Resistance-Associated Protein 2; D013448:Sulfobromophthalein; D010637:Phenolsulfonphthalein