Alpha-tocopherol in intravenous lipid emulsions imparts hepatic protection in a murine model of hepatosteatosis induced by the enteral administration of a parenteral nutrition solution.

Autor: Fell GL; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America., Anez-Bustillos L; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America., Dao DT; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America., Baker MA; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America., Nandivada P; Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America., Cho BS; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America., Pan A; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America., O'Loughlin AA; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America., Nose V; Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, United States of America., Gura KM; Department of Pharmacy, Boston Children's Hospital, Boston, Massachusetts, United States of America., Puder M; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2019 Jul 11; Vol. 14 (7), pp. e0217155. Date of Electronic Publication: 2019 Jul 11 (Print Publication: 2019).
DOI: 10.1371/journal.pone.0217155
Abstrakt: Intestinal failure-associated liver disease (IFALD) is a risk of parenteral nutrition (PN)-dependence. Intravenous soybean oil-based parenteral fat can exacerbate the risk of IFALD while intravenous fish oil can minimize its progression, yet the mechanisms by which soybean oil harms and fish oil protects the liver are uncertain. Properties that differentiate soybean and fish oils include α-tocopherol and phytosterol content. Soybean oil is rich in phytosterols and contains little α-tocopherol. Fish oil contains abundant α-tocopherol and little phytosterols. This study tested whether α-tocopherol confers hepatoprotective properties while phytosterols confer hepatotoxicity to intravenous fat emulsions. Utilizing emulsions formulated in the laboratory, a soybean oil emulsion (SO) failed to protect from hepatosteatosis in mice administered a PN solution enterally. An emulsion of soybean oil containing α-tocopherol (SO+AT) preserved normal hepatic architecture. A fish oil emulsion (FO) and an emulsion of fish oil containing phytosterols (FO+P) protected from steatosis in this model. Expression of hepatic acetyl CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ), was increased in animals administered SO. ACC and PPARγ levels were comparable to chow-fed controls in animals receiving SO+AT, FO, and FO+P. This study suggests a hepatoprotective role for α-tocopherol in liver injury induced by the enteral administration of a parenteral nutrition solution. Phytosterols do not appear to compromise the hepatoprotective effects of fish oil.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Specifically, a licensing agreement for the use of Omegaven® has been signed by Boston Children’s Hospital and Fresenius Kabi. Mark Puder and Kathleen Gura hold an issued patent on the treatment of parenteral nutrition-associated liver disease. The patent numbers are 9,566,260 and 9,629,821 under the name “Treatment and prevention of liver disease associated with parenteral nutrition (PN).” This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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