title: Organ heavy-metal accumulation during parenteral nutrition is associated with pathologic abnormalities in rats.
abstract: OBJECTIVE
  Metabolic bone disease, hepatic abnormalities, splenic insufficiency, and nephropathy have been associated with long-term total parenteral nutrition (TPN). We determined the heavy-metal contamination in TPN solutions and investigated whether it was associated with organ deposition and pathologic organ damage.
  
  
  METHODS
  Five representative TPN solutions (two adult standard solutions, one renal solution, and one standard pediatric solution to reflect clinical practice) and 28 TPN components were analyzed with inductively coupled plasma mass spectrometry. Twenty-six male Fisher 344 rats were assigned to two groups (chow/NaCl = 8 and TPN = 18). TPN or NaCl was infused at a rate of 50 mL/d. After 14 d, serum, femurs, spine, liver, kidneys, brain, spleen, and testes were analyzed for heavy-metal deposition by using inductively coupled plasma mass spectrometry. Tissues were fixed in formalin, sectioned, and stained with hematoxylin and eosin, periodic acid Schiff, and Masson's trichrome stain. Kidneys were fixed in gluteraldehyde for ultrastructural examination with scanning electron microscopy.
  
  
  RESULTS
  The predominant sources of contaminants in TPN were amino acids (Al, As, Cr, Ge, Pb, Sn), dextrose (As, Ba, Cr, Sn), Ca gluconate (Al), K2PO4 (Al), lipid emulsion (As, Sn), and vitamins (As). Significant variations in the level of contamination depended on TPN formulation and brand of constituents. In the kidney, Pb, Cr, and Mn concentrations were greater than in controls, although there was no correlation with serum creatinine. Hepatic Cr and Pb concentrations were greater in TPN rats, although there was no correlation with serum aspartate aminotransferase or total bilirubin. Splenic Ba, Cr, Ge, Pb, Mn, and Sn concentrations were greater in TPN rats. Only serum Cr concentration was significantly correlated with splenic concentration (r = 0.46, P = 0.04). Brain and serum Ba concentrations were significantly correlated (r = 0.60, P = 0.007). No significant correlations were observed between any other metal in serum and that metal's respective organ concentration. No increase in heavy-metal accumulation was seen in the femur, spine, or testis. There were no significant depositions of As, Cd, Hg, St, or V in any of the organs examined. Serum Al and Cr concentrations were significantly increased in TPN rats, although there was no correlation with tissue concentrations. No significant increases in heavy-metal concentrations in tissue or plasma were observed for any of the other metals measurable by inductively coupled plasma mass spectrometry. Histologically in the TPN group, 50% of the rats had mild to moderate hepatic steatosis and 33% to 50% developed renal morphologic abnormalities; brains and spleens remained histologically normal.
  
  
  CONCLUSIONS
  We found significant heavy-metal contamination of TPN solutions, and this contamination can lead to organ deposition and subsequent histologic abnormalities.
authors.affiliation: Division of Gastroenterology and Hepatology, Northwestern University Medical School, Chicago, Illinois, USA. a-buchman@nwu.edu
authors.forename: A L
authors.initials: AL
authors.lastname: Buchman
authors.forename: M
authors.initials: M
authors.lastname: Neely
authors.forename: V B
authors.initials: VB
authors.lastname: Grossie
authors.forename: L
authors.initials: L
authors.lastname: Truong
authors.forename: E
authors.initials: E
authors.lastname: Lykissa
authors.forename: C
authors.initials: C
authors.lastname: Ahn
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004340:Drug Contamination / Q000517:prevention & control*; D005269:Femur / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D013058:Mass Spectrometry; D019216:Metals, Heavy / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008855:Microscopy, Electron, Scanning; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D012996:Solutions / Q000032:analysis; D013131:Spine / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D019216:Metals, Heavy; D012996:Solutions