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Hepatic Abnormalities Associated with Aluminum Loading in Piglets

Divisions of Pediatrics and Pathology, City of Hope National Medical Center, Duarte, California, Departments of Pediatrics and Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of California Medical Center. San Francisco, California, Center for Electron Microscopy and Microanalysis, University of Southern California. Los Angeles, California, Medical and Research Services, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, U.S.D.A. National Animal Disease Center, Ames, Iowa

Aileen B. Sedman

Divisions of Pediatrics and Pathology, City of Hope National Medical Center, Duarte, California, Departments of Pediatrics and Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of California Medical Center. San Francisco, California, Center for Electron Microscopy and Microanalysis, University of Southern California. Los Angeles, California, Medical and Research Services, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, U.S.D.A. National Animal Disease Center, Ames, Iowa

Melvin B. Heyman

Divisions of Pediatrics and Pathology, City of Hope National Medical Center, Duarte, California, Departments of Pediatrics and Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of California Medical Center. San Francisco, California, Center for Electron Microscopy and Microanalysis, University of Southern California. Los Angeles, California, Medical and Research Services, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, U.S.D.A. National Animal Disease Center, Ames, Iowa

Gopal Marathe

Divisions of Pediatrics and Pathology, City of Hope National Medical Center, Duarte, California, Departments of Pediatrics and Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of California Medical Center. San Francisco, California, Center for Electron Microscopy and Microanalysis, University of Southern California. Los Angeles, California, Medical and Research Services, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, U.S.D.A. National Animal Disease Center, Ames, Iowa

Hector A. Battifora

Divisions of Pediatrics and Pathology, City of Hope National Medical Center, Duarte, California, Departments of Pediatrics and Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of California Medical Center. San Francisco, California, Center for Electron Microscopy and Microanalysis, University of Southern California. Los Angeles, California, Medical and Research Services, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, U.S.D.A. National Animal Disease Center, Ames, Iowa

Jack L. Worrall

Divisions of Pediatrics and Pathology, City of Hope National Medical Center, Duarte, California, Departments of Pediatrics and Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of California Medical Center. San Francisco, California, Center for Electron Microscopy and Microanalysis, University of Southern California. Los Angeles, California, Medical and Research Services, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, U.S.D.A. National Animal Disease Center, Ames, Iowa

Ronald L. Horst

Divisions of Pediatrics and Pathology, City of Hope National Medical Center, Duarte, California, Departments of Pediatrics and Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of California Medical Center. San Francisco, California, Center for Electron Microscopy and Microanalysis, University of Southern California. Los Angeles, California, Medical and Research Services, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, U.S.D.A. National Animal Disease Center, Ames, Iowa

George J. Brewer

Divisions of Pediatrics and Pathology, City of Hope National Medical Center, Duarte, California, Departments of Pediatrics and Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of California Medical Center. San Francisco, California, Center for Electron Microscopy and Microanalysis, University of Southern California. Los Angeles, California, Medical and Research Services, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, U.S.D.A. National Animal Disease Center, Ames, Iowa

Nancy L. Miller

Divisions of Pediatrics and Pathology, City of Hope National Medical Center, Duarte, California, Departments of Pediatrics and Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of California Medical Center. San Francisco, California, Center for Electron Microscopy and Microanalysis, University of Southern California. Los Angeles, California, Medical and Research Services, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, U.S.D.A. National Animal Disease Center, Ames, Iowa

Allen C. Alfrey

Divisions of Pediatrics and Pathology, City of Hope National Medical Center, Duarte, California, Departments of Pediatrics and Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of California Medical Center. San Francisco, California, Center for Electron Microscopy and Microanalysis, University of Southern California. Los Angeles, California, Medical and Research Services, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, U.S.D.A. National Animal Disease Center, Ames, Iowa

Cholestasis is a common complication of total parenteral nutrition (TPN) in infants. A contributing factor to the hepatic dysfunction may be a contaminant of the TPN solution, such as aluminum, that accumulates in liver and may act as a hepatotoxin. To study the hepatic effects of aluminum, growing piglets were given daily intravenous injections of aluminum, 1.5 mg/kg, for 50 days; pair-fed controls were given heparinized saline. At sacrifice, liver and serum were obtained. Liver was analyzed for histopathology and for aluminum content and localization. The hepatocyte lysosomes of the experimental group showed aluminum peaks by x-ray microanalysis, whereas the control group did not. No differences in ultrastructure were noted between the two groups when examined by electron microscopy. Mean serum total bile acid levels (27.8 ± 15.9 SD vs 6.3 ± 1.5 µmol/liter, p < 0.05), mean alkaline phosphatase (309 ± 108 vs 180 ± 27 lU/liter, p = NS), and mean hepatic copper content (24.8 ± 4.5 vs 14.4 ± µg/g dry weight, p < 0.01), were elevated in the aluminum-loaded piglets, indicating that cholestasis may have been produced. Also, a small but significant reduction in serum levels of 25 hydroxyvitamin D was found in the aluminum-loaded piglets, suggesting that vitamin D hydroxylation may be impaired. Inasmuch as lysosomal contents are excreted into the bile, aluminum accumulation in lysosomes may alter lysosomal function and possibly affect bile flow or content. (Journal of Parenteral and Enteral Nutrition 11:293-297, 1987)

Journal of Parenteral and Enteral Nutrition, Vol. 11, No. 3, 293-297 (1987)
DOI: 10.1177/0148607187011003293


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