• manganese;
  • bilirubin;
  • intrahepatic cholestasis;
  • bile canaliculi;
  • microvilli;
  • vacuoles

ABSTRACT— Small doses of manganese or bilirubin administered alone to rats produce no morphologic alterations in the hepatocytes. However, combination of both treatments produced a rapid and severe decrease in bile flow that was paralleled by the appearance and aggravation of the cholestatic lesion: bile canaliculi progressively lost their microvilli; vacuolization occurred in the pericanalicular area and subsequently in the cytoplasm. When bile flow returned to normal, or when cholestasis was prevented by an injection of sulfobromophthalein or a pretreatment with phalloidin, no cholestatic signs were observed. A close correlation appears to exist between the presence of morphologic alterations and the decrease of bile flow in manganese-bilirubin cholestasis.