BILIARY-EXCRETION OF COPPER, MANGANESE, AND HORSERADISH-PEROXIDASE INEISAI HYPERBILIRUBINEMIC MUTANT RATS (EHBRS) WITH DEFECTIVE BILIARY-EXCRETION OF GLUTATHIONE

A mixture of copper (Cu) (0.38 mg/kg), manganese (Mn) (0.038 mg/kg), a nd horseradish peroxidase (HRP) (5.0 mg/kg) was injected intravenously (iv) into mature Eisai hyperbilirubinemic rats (EHBRs) and Sprague-Da wley rats (SDRs). Bile was collected at 10-min intervals before and af ter the injection, under anesthesia. The Liver, kidneys, and blood wer e removed 40 min after the injection. The serum-conjugated bilirubin c oncentration was 0.85 mg/dL in the EHBRs, but was below detection limi ts in the SDRs. The bile-reduced glutathione (GSH) concentration was m uch lower in the EHBRs (0.04 mg/mL) than in the SDRs (1.30 mg/mL). How ever, the hepatic GSH concentration was about 1.6 times higher in EHBR s (2.26 mg/g Liver) than in SDRs (1.43 mg/g liver). The low excretion of biliary GSH was not caused by the activity of GGT in the liver, sin ce there was no significant difference in the activity between the two groups (5.8 +/- 3.4 and 4.6 +/- 2.4 mu mol p-nitroaniline/g protein/3 0 min in SDR and EHBR groups, respectively). There was a delay of init ial biliary excretion of Cu in EHBRs compared to SDRs. The biliary con centration of Mn was slightly lower in EHBRs than in SDRs. Forty min a fter the injection of metals, however, there was no difference between hepatic concentrations of the two metals in the two groups. Our resul ts suggest that abnormal deposition of the two metals is not observed naturally in EHBRs. Injected HRP was excreted rapidly and notably in t he EHBRs compared to SDRs. Furthermore, the biliary concentration of b eta-N-acetyl-D-glucosaminidase (beta-NAG) was significantly higher in EHBRs than in SDRs. Rapid biliary excretion of Cu, but not of Mn, may be related to the hepatobiliary transport of GSH, but the transport an d lysosomal function do not originally regulate the biliary excretion of Cu.