title: Hepatic indicators of oxidative stress and tissue damage accompanied by systemic inflammation in rats following a 24-hour infusion of an unstable lipid emulsion admixture.
abstract: BACKGROUND
  Use of lipid emulsions in parenteral nutrition therapy is an important source of daily energy in substitution of potentially harmful glucose calories when given in excess in the intensive care unit. When added to parenteral nutrition (PN) admixtures as a total nutrient admixture (TNA), the stability and safety of the emulsion may be compromised. Development of a rat model of a stable vs unstable lipid infusion would enable a study of the potential risk.
  
  
  METHODS
  Prospective, randomized, controlled study.
  
  
  METHODS
  Surgical placement of a jugular venous catheter for the administration of TNAs was performed. Two groups were studied: a stable or s-TNA (n = 16) and an unstable or u-TNA (n = 17) as a 24-hour continuous infusion. Stability of TNAs was determined immediately before and after infusion using a laser-based method approved by the United States Pharmacopeia.
  
  
  RESULTS
  Blood levels of aspartate aminotransferase, glutathione-S-transferase, and C-reactive protein were significantly elevated in u-TNA vs s-TNA (P < .05). Also, liver tissue concentrations of malondialdehyde were significantly higher in the u-TNA group (P < .05), and triglyceride tissue levels were also higher in u-TNA and approached statistical significance (P = .077).
  
  
  CONCLUSIONS
  Unstable lipid infusions over 24 hours produce evidence of hepatic accumulation of fat associated with oxidative stress, liver injury, and a low-level systemic inflammatory response.
authors.affiliation: Harvard Medical School, Boston, MA, USA. ddriscol@bidmc.harvard.edu
authors.forename: David F
authors.initials: DF
authors.lastname: Driscoll
authors.forename: Pei-Ra
authors.initials: PR
authors.lastname: Ling
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andersson
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Bistrian
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D004355:Drug Stability; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D005982:Glutathione Transferase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D023421:Models, Animal; D018384:Oxidative Stress; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005217:Fat Emulsions, Intravenous; D014280:Triglycerides; D008315:Malondialdehyde; D002097:C-Reactive Protein; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases