Preoperative short-term parenteral administration of polyunsaturated fatty acids ameliorates intestinal inflammation and postoperative ileus in rodents.
OBJECTIVE
Abdominal surgery results in an inflammation of the intestinal muscularis externa (ME), subsequently leading to postoperative ileus (POI). Polyunsaturated fatty acids (PUFA) are known to modulate inflammation. The aim of this study was to analyze the effect of preoperative parenteral administration of marine (n-3) or soybean (n-6) PUFA lipid emulsions (PUFA-LE) on POI and tissue fatty acid profiles.


METHODS
Rodents underwent intestinal manipulation (IM) after 5 days of parenteral administration of 10-mL/kg body weight saline, (n-3), or (n-6) PUFA-LE. Sham animals received saline treatment without IM. In rats, postoperative inflammation was quantified by ME neutrophil levels and NO production in organ culture, and ME function was determined by an in vitro contractility measurement. Additionally, in vivo gastrointestinal transit (GIT) was analyzed in mice. Lipopolysaccharide-induced IL-6 expression of rat bone marrow-derived mononuclear cells and ME was analyzed. Fatty acids were measured by gas chromatography in rat blood, bone marrow cells, and ME.


RESULTS
The (n-3) PUFA-LE reduced neutrophil levels and NO production after IM and improved in vitro jejunal contractility and GIT time. The (n-6) PUFA-LE significantly reduced postoperative inflammation and tended to improve intestinal motility (P < 0.06). Interestingly, (n-6) PUFA-LE significantly reduced the levels of arachidonic acid in ME (-63%), while (n-3) PUFA-LE reduced arachidonic acid (-20%) and additionally raised EPA (+550%).


CONCLUSIONS
Short-term preoperative parenteral administration of (n-3) or (n-6) PUFA-LE significantly alters tissue-specific fatty acid profiles. Preoperative parenteral PUFA-LE supplementation, preferably by marine (n-3) PUFA, ameliorates postoperative intestinal inflammation and dysmotility and could be a promising therapeutic option in POI prophylaxis.
Department of Surgery, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
Sven
S
Wehner
Katharina
K
Meder
Tim O
TO
Vilz
Birgit
B
Alteheld
Peter
P
Stehle
Thomas
T
Pech
Joerg C
JC
Kalff
D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004751:Enteritis / Q000473:pathology / Q000517:prevention & control*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D045823:Ileus / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D007263:Infusions, Parenteral; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D007430:Intraoperative Care / Q000379:methods; D007813:Laparotomy / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D011183:Postoperative Complications / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D016896:Treatment Outcome
D016207:Cytokines; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D009569:Nitric Oxide