METABOLISM OF DIGITOXIN IN THE ISOLATED PERFUSED RAT-LIVER - EFFECT OF SPIRONOLACTONE PRETREATMENT

  • 1 January 1979
    • journal article
    • research article
    • Vol. 7  (5) , 280-284
Abstract
Livers from control or spironolactone-treated rats were perfused for 90 min with 30% rat blood and 3H-digitoxin. At several time periods throughout perfusation, bile was collected and a sample of blood was removed from the perfusate. Extractions were performed on blood and bile to determine the amount of polar and nonpolar metabolites at 60 min. Polar metabolites were cleaved with .beta.-glucuronidase and high-pressure liquid chromatography was used to separate the resultant nonpolar metabolites from blood and bile cleaved with .beta.-glucuronidase. Biliary excretion and perfusate disappearance of 3H-digitoxin were significantly increased in livers taken from spironolactone-pretreated animals. Both polar and nonpolar metabolites in bile were significantly increased in pretreated animals. The majority of polar metabolites produced by livers from both treated and nontreated animals were readily cleaved with .beta.-glucuronidase. Both biliary excretion and metabolic pattern, obtained from the studies in an isolated perfused rat liver, mimic those seen in the intact rat. The isolated perfused rat liver can be used as a model for in vivo studies of cardiac glycoside metabolism.