Bile Secretion of Trace Elements in Rats with a Congenital Defect in Hepatobiliary Transport of Glutathione

Abstract

Bile secretion of trace elements, analyzed by proton-induced x-ray emission, was studied in rats with a congenital defect in hepatobiliary transport of organic anions [Groningen Yellow (GY) rats], in which the process of bile secretion resembles that of the neonatal period. Bile flow (-41%) and biliary glutathione secretion (-99%) were drastically impaired in GY rats compared with controls. Plasma concentrations of all detectable trace elements (Fe, Cu, Zn, Mo, Br, and Se), as well as that of simultaneously determined Ca, were similar in GY and age-matched control Wistar rats. Bile concentrations of Fe, Mo, Br, and Ca were also similar in both groups, resulting in a approximately 40% reduction of their secretion rates in GY rats. The concentrations of Zn (-62%) and Mn (-64%) were significantly lower in GY rats in contrast to that of Cu, which was 50% higher. Se could not be detected in bile of either group. Recovery in bile (% dose/3 h) after i.v. injection of MnCl2, CuSO4, or SeO2 (1 mg metal/kg) was lower in GY rats than in controls: Mn, 26 and 35%; Cu, 2.6 and 5%; and Se, 1.5 and 5%, respectively. Injection of ZnSO4 did not lead to increased Zn secretion in GY rats, and only 1.1% of the dose was recovered in controls. Thus, the hepatic handling of different endogenous and exogenously administered trace metals is affected to a variable extent in the GY rat. For a number of metals (e.g. Fe, Mo), this may be related to the reduced bile flow; for others (e.g. Zn, Mn, Cu), other regulatory factors appear to be responsible.