Increased biliary transferrin excretion following parenteral aluminium administration to rats.
Aluminium accumulates in the livers of patients receiving either parenteral nutrition or haemodialysis. When given parenterally to rats, aluminium causes cholestasis. However, the mechanism of hepatic aluminium uptake and the fate of aluminum in the liver are poorly understood. We examined the effect of parenteral aluminium administration on biliary excretion 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. Biliary total protein concentration and IgA/total protein were unaffected by up to 14 days of parenteral aluminium administration. However, biliary transferrin excretion increased with duration of aluminum administration 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 were not different from controls. Since biliary transferrin is normally derived from the serum, it is likely that aluminum promotes hepatocellular uptake of transferrin and that aluminum enters the hepatocyte bound to transferrin. We postulate that transferrin may direct aluminum to intracellular sites where its toxic effects would be minimized.
Klein
G L
GL
Department of Paediatrics, University of Texas Medical Branch, Galveston 77555-0352.
Goldblum
R M
RM
Moslen
M T
MT
Pyron
D L
DL
Mann
P A
PA
Lee
T C
TC
Alfrey
A C
AC
D000410:Alanine Transaminase / Q000097:blood; D000535:Aluminum / Q000008:administration & dosage*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000097:blood; D002712:Chlorides / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D007070:Immunoglobulin A / Q000032:analysis; D007263:Infusions, Parenteral; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014168:Transferrin / Q000378:metabolism*
D017607:Aluminum Compounds; D001647:Bile Acids and Salts; D002712:Chlorides; D007070:Immunoglobulin A; D014168:Transferrin; D000077410:Aluminum Chloride; D000535:Aluminum; D000410:Alanine Transaminase