Effects of Ethanol and Taurocholate on Bromsulphthalein Excretion by the Isolated,Perfused Liver 1

Abstract

Previous studies have shown that perfusion of the isolated rat liver with ethanol leads to a marked reduction of bile flow and bromsulphthalein (BSP) biliary excretion (1). It was further demonstrated that these phenomena closely paralleled each other permitting the inference that ethanol could act on the liver as a direct “cholestatic” agent thereby decreasing the transport of foreign dye into the bile. It has been proposed that BSP effectively competes with bile salts for excretion in bile (2-5). In the perfused rat liver, BSP added as a single bolus significantly decreases the rate of bile flow (6) suggesting perhaps a direct competition with the bile acids.

Taurocholate has been shown to increase both the rate of bile flow and the biliary excretion of BSP by dogs in vivo (5) and in the isolated rat liver (7). The present study demonstrates that perfusion of the isolated liver with taurocholate and ethanol, leads to a dissociation between the rate of bile flow and the biliary excretion of BSP.

Experimental. Female, unfasted Sprague-Dawley rats (220-280 g) were anaesthesized with Sodium Pentobarbital (Nembutal, Abbott, 5 mg/100 g body weight). Following cannulations of the bile duct and the portal vein, the liver was excised and perfused according to methods that have been described (1). The perfusion medium consisted of Krebs-Henseleit buffer, gassed with a mixture of O₂:CO₂ (95:5, vol %, pH = 7.4 and contained, per 100 ml, 240 mg glucose, 2.5 g bovine albumin (35% sol., Pentex Biochemicals), and 3,000 USP units of heparin (Liquaemin, Organon). 250 mM/liter of ethanol were added 30 min after beginning the perfusion. An infusion of simultaneous Sodium Taurocholate (Mann Research Labs.) and BSP (Hynson, Westcott, & Dunning, Inc.)