Modification of biliary tree permeability in rats treated with a manganese-bilirubin combination

Previous studies in this laboratory demonstrated incorporation of manganese (Mn) and bilirubin (BR) in rat liver bile canalicular membrane (BCM) following a cholestatic regimen composed sequentially of Mn plus BR. The present study investigates biliary tree permeability using segmented retrograde intrabiliary injection (SRII) with [3H]mannitol and [3H]inulin as marker substances. Male Sprague-Dawley rats were given the following iv: (a) Mn (high and low dose), (b) BR, (c) sulfobromophthalein (BSP), (d) Mn-BSP-BR, (e) MnBR. Results obtained with mannitol showed a approximately 63% decrease (p less than 0.05) in marker recovery following administration of MnBR combination. While BSP alone had no effect on mannitol recovery, BSP abolished the MnBR response when administered in the Mn-BSP-BR sequence. With inulin, Mn (high dose), MnBR, and Mn-BSP-BR all produced a approximately 45% decrease (p less than 0.05) in recovery, while BSP or BR alone caused a approximately 25% decrease (p less than 0.05). Mn (low dose) was without effect. These results and others obtained when the time pattern of the MnBR treatment was modified suggest: (1) MnBR treatment increases biliary tree permeability by altering both BCM and the junctional complex; (2) BCM alteration is probably the more critical event, since BSP, which protects against MnBR cholestasis, protected against the MnBR-induced change in mannitol recovery, but exerted no effect on inulin recovery.