INCREASED BILIARY TRANSFERRIN EXCRETION FOLLOWING PARENTERAL ALUMINUMADMINISTRATION TO RATS

Aluminum accumulates in the livers of patients receiving either parent eral nutrition or haemodialysis. When given parenterally to rats, alum inum causes cholestasis. However, the mechanism of hepatic aluminum up take and the fate of aluminum in the liver are poorly understood. We e xamined the effect of parenteral aluminum administration on biliary ex cretion of transferrin, the major circulating aluminum-binding protein . Male Wistar rats were given parenterally aluminum 5 mg/kg/day for 1- 14 days. Bile was collected for 3 hr at the end of the study period. B iliary total protein concentration and IgA/total protein were unaffect ed by up to 14 days of parenteral aluminum administration. However, bi liary transferrin excretion increased with duration of aluminum admini stration up to five-fold by day 14. Biliary transferrin concentration and transferrin/total protein was higher in aluminum treated rats than controls after 7 and 14 days of study. Hepatic aluminum concentration reached a maximum after 4 days of parenteral aluminum administration, at which time serum bile acid and alanine amino transferase values we re not different from controls. Since biliary transferrin is normally derived from the serum, it is likely that aluminum promotes hepatocell ular uptake of transferrin and that aluminum enters the hepatocyte bou nd to transferrin. We postulate that transferrin may direct aluminum t o intracellular sites where its toxic effects would be minimized.