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Characterization of the effects of erythromycin estolate and erythromycin base on the excretory function of the isolated rat liver.

Abstract：

:To investigate the mechanisms of erythromycin cholestasis, the effects of erythromycin estolate (EE) on the excretory function of the isolated perfused rat liver and on liver plasma membrane (LM) preparations were studied and compared to those of erythromycin base (EB) and lauryl sulfate (LS), added alone or in combination. EE (at 125 to 200 microM) caused dose-dependent reductions of bile and perfusate flows, bile acid (BA) excretion, and biliary BA concentration. The alterations of the excretory function were only in part due to the decreased perfusate flow. In contrast, both 200 and 300 microM concentrations of EB elicited similar choleretic responses, which were presumably related to the osmotic activity of the drug excreted in the bile. LS did not affect hepatic excretory functions. However, the simultaneous addition of EB and LS resulted in a rate of bile flow lower than that observed with EB alone. EE, but not EB, increased canalicular permeability to [14C]sucrose as measured by bile to plasma (B:P) ratio. Neither drugs altered [14C]erythritol B:P ratio. In LM preparations both Na+,K+- and Mg2+-ATPase activities were inhibited in a dose-dependent manner by EE, but not by EB. The data suggest that EE could affect bile flow by inhibiting cotransport of Na+ and BA and by altering LM permeability and support the view that the effect of erythromycins on the liver may be related to their surface activity.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Gaeta GB,Utili R,Adinolfi LE,Abernathy CO,Giusti G

doi

10.1016/0041-008x(85)90074-2

subject

Has Abstract

pub_date

1985-09-15 00:00:00

pages

185-92

issue

2

eissn

0041-008X

issn

1096-0333

pii

0041-008X(85)90074-2

journal_volume

80

pub_type

杂志文章

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