title: A Comparison of Fish Oil Sources for Parenteral Lipid Emulsions in a Murine Model.
abstract: Fat emulsions are important components of parenteral nutrition (PN). Fish oil (FO) emulsions reverse cholestasis in PN-associated liver disease. There are 2 FO monographs. One is "FO; rich in omega-3 fatty acids" (NFO). The other, "omega-3 acids," (PFO), is enriched in omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The purpose of this study is to compare the effects of 20% NFO and PFO emulsions produced in the laboratory in a murine model.
  
  
  
  Emulsions were compounded containing different oils: soybean oil (SO), NFO, and two PFOs differing in percentage of fatty acids as triglycerides (PFO66 and PFO90). Chow-fed mice received saline, one of the above emulsions, or a commercial FO (OM) intravenously (2.4 g/kg/day) for 19 days. On day 19, animals were euthanized. Livers, spleens, and lungs were procured for histologic analysis.
  
  
  
  OM, SO, NFO, and PFO90 were well-tolerated clinically. PFO66 resulted in tachypnea and lethargy for ~1 minute following injections. At euthanasia, PFO66 and PFO90 groups had organomegaly. Histologically, these groups had splenic and hepatic fat-laden macrophages, and lungs had scattered fat deposits. Other groups had normal organs.
  
  
  
  PFO emulsions present an attractive possibility for improving inflammation in PN-dependent patients by concentrating anti-inflammatory EPA and DHA. However, 20% PFO emulsions were poorly tolerated and precipitated adverse end organ sequelae, suggesting that they may not be safe. Development of novel manufacturing methods may achieve safe 20% PFO parenteral emulsions, but by established formulation methods, these emulsions were clinically suboptimal despite meeting pharmacopeial standards.
authors.affiliation: 1 Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Gillian L
authors.initials: GL
authors.lastname: Fell
authors.affiliation: 1 Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Bennet S
authors.initials: BS
authors.lastname: Cho
authors.affiliation: 1 Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Pan
authors.affiliation: 2 Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Vania
authors.initials: V
authors.lastname: Nose
authors.affiliation: 1 Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Anez-Bustillos
authors.affiliation: 1 Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Duy T
authors.initials: DT
authors.lastname: Dao
authors.affiliation: 1 Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Baker
authors.affiliation: 3 Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Prathima
authors.initials: P
authors.lastname: Nandivada
authors.affiliation: 4 Department of Pharmacy, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gura
authors.affiliation: 1 Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Puder
mesh_terms: D000818:Animals; D004281:Docosahexaenoic Acids / Q000032:analysis; D015118:Eicosapentaenoic Acid / Q000032:analysis; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D015525:Fatty Acids, Omega-3 / Q000032:analysis; D005395:Fish Oils / Q000008:administration & dosage / Q000737:chemistry*; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010288:Parenteral Nutrition / Q000009:adverse effects; D013024:Soybean Oil; D013154:Spleen / Q000187:drug effects; D014280:Triglycerides
chemical_list: D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D013024:Soybean Oil; D015118:Eicosapentaenoic Acid
keywords: USP 729; fish oil; intestinal failure; parenteral lipid emulsions; parenteral nutrition–associated liver disease