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

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Abstract

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 ∼63% decrease (p < 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 ∼45% decrease (p < 0.05) in recovery, while BSP or BR alone caused a ∼25% decrease (p < 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.

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    Supported by the Medical Research Council of Canada.

    ☆☆

    Presented in part at the 24th Annual Meeting of the Society of Toxicology, March 1985. San Diego, Calif.

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