Aluminum-associated hepatobiliary dysfunction in rats: relationships to dosage and duration of exposure.
Aluminum may contaminate parenteral nutrition solutions and accumulate in bone and liver of patients receiving this therapy. Although aluminum exposure is associated with low-turnover osteomalacia, there are few studies of hepatotoxicity. We therefore studied the effects of aluminum given to rats on total serum bile acid concentration and bile flow to determine if aluminum administration could produce abnormalities. Aluminum was given intravenously as follows: 5 mg/kg daily for 7 or 14 days and 1 mg/kg for 14 days. Hepatic aluminum was high in treated rats and undetectable in controls. Total serum bile acid concentrations were significantly higher in treated rats than in pair-fed controls with higher concentrations after 14 days than after 7 days. Bile flow was reduced by 33% in rats given 5 mg/kg but not in rats given 1 mg/kg. Hepatic aluminum correlated inversely with bile flow but not with serum bile acid concentration. Aluminum exposure in rats is associated with elevated serum bile acid concentration and diminished bile flow and may play a role in the pathogenesis of parenteral nutrition-induced hepatobiliary dysfunction.
Klein
G L
GL
Department of Pediatrics, University of Texas Medical Branch, Galveston 77550-2776.
Heyman
M B
MB
Lee
T C
TC
Miller
N L
NL
Marathe
G
G
Gourley
W K
WK
Alfrey
A C
AC
D000535:Aluminum / Q000378:metabolism / Q000633:toxicity*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism / Q000633:toxicity*; D002779:Cholestasis / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D017607:Aluminum Compounds; D001647:Bile Acids and Salts; D002712:Chlorides; D000077410:Aluminum Chloride; D000535:Aluminum