Manganese-bilirubin cholestasis. Further studies in pathogenesis

To further delineate the mechanism of manganese-bilirubin cholestasis, studies were done to determine: the structural status of the canalicular tight junctions in the model, and the effect of the lack of bilirubin conjugation. The results indicate that canalicular tight junction alterations characteristic of many types of cholestasis develop in this model and that bilirubin conjugation is not a requisite for the cholestatic effect of bilirubin to occur. It is unclear whether the tight junction alterations are the cause of the cholestasis or either secondary effects of the cholestasis or associated noncausal occurrences. The fact that bilirubin does not need to be conjugated in order to effect cholestasis confirms that the cholestasis is due to intrahepatocytic (as opposed to intracanalicular) effects, and may be useful in determining the precise locus and nature of these effects.