The effects of amphotericin B (AmB) on the hepatic excretory function and the colloid clearance capacity were investigated in the perfused rat liver. AmB at 5 or 10 microM caused dose-dependent reductions in bile and perfusate flow rates and in biliary bile acid (BA) excretion. BA concentration in bile tended to increase, due to a prominent reduction in bile water induced by the drug. At 5 microM, AmB also caused an increase in [14C]sucrose clearance by the liver and a release of hepatocytic enzymes into the perfusate. These alterations were not related to the decrease in the perfusate flow induced by AmB. In addition, the drug, at 5 microM, caused a significant decrease in the colloidal carbon clearance by the liver. In this case also, the effect was independent of the reduction in the perfusate flow induced by the drug. The toxic effects of AmB on the rat liver could be interpreted as a derangement of the cell membrane functional integrity, which causes cholestasis, enzyme leakage and an impairment of the reticuloendothelial system function. This latter effect deserves careful evaluation of its clinical implications.
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