INCREASED BILIARY TRANSFERRIN EXCRETION FOLLOWING PARENTERAL ALUMINUM ADMINISTRATION TO RATS

被引:10
作者
KLEIN, GL
GOLDBLUM, RM
MOSLEN, MT
PYRON, DL
MANN, PA
LEE, TC
ALFREY, AC
机构
[1] VET ADM MED CTR,MED SERV,DENVER,CO 80220
[2] VET ADM MED CTR,RES SERV,DENVER,CO 80220
[3] UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77555
[4] UNIV COLORADO,SCH MED,DENVER,CO 80202
来源
PHARMACOLOGY & TOXICOLOGY | 1993年 / 72卷 / 06期
关键词
D O I
10.1111/j.1600-0773.1993.tb01347.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aluminum accumulates in the livers of patients receiving either parenteral nutrition or haemodialysis. When given parenterally to rats, aluminum causes cholestasis. However, the mechanism of hepatic aluminum uptake and the fate of aluminum in the liver are poorly understood. We examined the effect of parenteral aluminum 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 aluminum 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.
引用
收藏
页码:373 / 376
页数:4
相关论文
共 18 条
[1]  
ABREO K, 1991, J AM SOC NEPHROL, V1, P1299
[2]  
BIDLACK WR, 1987, DRUG NUTR INTERACT, V5, P33
[3]   ORIGIN AND NATURE OF PROTEINS OF BILE .2. COMPARATIVE ANALYSIS OF SERUM, HEPATIC LYMPH AND BILE PROTEINS IN DOG [J].
DIVE, C ;
NADALINI, RA ;
VAERMAN, JP ;
HEREMANS, JF .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1974, 4 (04) :241-246
[4]  
GALLE P, 1982, NOUV PRESSE MED, V11, P1123
[5]  
HEUBERS HA, 1987, PHYSIOL REV, V67, P520
[6]   INVIVO INTERACTIONS OF ALUMINUM WITH HEPATIC CYTOCHROME-P-450 AND METALLOTHIONEIN [J].
JEFFERY, EH ;
JANSEN, HT ;
DELLINGER, JA .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1987, 8 (04) :541-548
[7]  
Klein G L, 1982, Trans Assoc Am Physicians, V95, P155
[8]   HEPATIC ALUMINUM ACCUMULATION IN CHILDREN ON TOTAL PARENTERAL-NUTRITION [J].
KLEIN, GL ;
BERQUIST, WE ;
AMENT, ME ;
COBURN, JW ;
MILLER, NL ;
ALFREY, AC .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 1984, 3 (05) :740-743
[9]   ALUMINUM-ASSOCIATED HEPATOBILIARY DYSFUNCTION IN RATS - RELATIONSHIPS TO DOSAGE AND DURATION OF EXPOSURE [J].
KLEIN, GL ;
HEYMAN, MB ;
LEE, TC ;
MILLER, NL ;
MARATHE, G ;
GOURLEY, WK ;
ALFREY, AC .
PEDIATRIC RESEARCH, 1988, 23 (03) :275-278
[10]   ALTERED GLYCINE AND TAURINE CONJUGATION OF BILE-ACIDS FOLLOWING ALUMINUM ADMINISTRATION TO RATS [J].
KLEIN, GL ;
LEE, TC ;
HEYMAN, MB ;
RASSIN, DK .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 1989, 9 (03) :361-364