Phalloidin-induced cholestasis: a microfilament-mediated change in junctional complex permeability

Abstract

Phalloidin, administered to male rats for 7 days (500 microgram per kg/day), increased the mean hepatic content of filamentous actin. Both bile flow and bile acid excretion diminished proportionally, whereas the bile-to-plasma ratios of [3H]inulin and [14C]sucrose increased significantly from 0.08 and 0.16 in controls to 0.37 and 0.69, respectively, in phalloidin-treated animals. Simultaneously, junctional permeability was altered as noted by the free penetration of ionic lanthanum into the zonula occludens and bile canaliculus. Freeze-fracture replicas of the junctional complex revealed rearrangements of the junctional elements and regions in which only a single element separated the canaliculus from the lateral intercellular space. These findings suggest that microfilaments influence the permeability of "tight junctions" between hepatocytes and that bile constituents might reflux from the canaliculus to the intercellular space in phalloidin-induced cholestasis.