Abstract
Abstract
Chlorpromazine at a concentration of 250 μM and estradiol-17β-D-glucuronide at 17.5 μM on infusion led to a sharp reduction in bile flow by the in vitro perfused rat liver. This was accompanied by fragmentation and a loss of canalicular microvilli, dilatation of canaliculi, and thickening of pericanalicular ectoplasm. Less prominent were the smooth endoplasmic reticulum dilatation, lysosomal lamination, and the appearance of amorphous bile in hepatocyte cytoplasm. The bile flow and electron microscopy appearance were restored to normal by infusion of tauroursodeoxycholate in a concentration of 5 μmol/min for the estradiol-17β-D-glucuronide-induced cholestasis and 1.5 μmol/min for the chlorpromazine-induced cholestasis. Changes in ultrastructure paralleled changes in bile flow. These observations demonstrate the feasibility of electron microscopy studies on the perfused liver, and the rapidity with which cholestatic changes appear.
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