Increased paracellular permeability in intrahepatic cholestasis induced by carmustine (BCNU) in rats
作者： Herbert Krell , Hartmut Fromm , Robert E. Larson
DOI: 10.1016/0016-5085(91)90476-2
关键词:
摘要: Carmustine [i.e., 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)] is a drug with cholestatic potency both in experimental animals and humans. To study the mechanisms involved development of hepatic lesions, early changes liver function rats pretreated were investigated. Dosages sampling times that did not result hepatocellular injury, as indicated by release marker enzymes, applied. In isolated perfused livers from rats, bile flow maximal secretion rate taurocholate decreased. An increase biliary [14C]sucrose clearance suggested enhanced permeability tract was correlated increased inorganic phosphate concentration bile. assess contribution paracellular transcellular pathways sucrose, access into analyzed off-kinetics after omission radioactive perfusion medium. improved method developed to quantitate applying classical equation portion sucrose clearance. With this it shown pretreatment BCNU resulted an diffusion convection perfusate Accordingly, fast horseradish peroxidase facilitated BCNU-treated rats. The results indicate alteration may contribute hepatotoxic lesions caused BCNU. It inert solute can be used if fraction determined.
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