n-3 Polyunsaturated fatty acid-enriched diet does not protect from liver injury but attenuates mortality rate in a rat model of systemic endotoxemia.
OBJECTIVE
We investigated the potential of dietary fish oil containing n-3 polyunsaturated fatty acids to attenuate hepatic injury and mortality rate of rats in response to systemic endotoxemia.


METHODS
Prospective, randomized, controlled animal study.


METHODS
University laboratory.


METHODS
A total of 43 male Sprague Dawley rats.


METHODS
Rats were fed either fish oil supplement or regular standard lab chow. After 8 wks of feeding, each diet group was subjected to a single exposure of lipopolysaccharide (Escherichia coli, 10 mg/kg intravenously) or saline. Hepatic microvascular response and liver injury were assessed by in vivo analysis of Kupffer cell phagocytic activity, leukocyte-endothelial cell interaction, nutritive sinusoidal perfusion failure, and parenchymal cell apoptosis (intravital fluorescence epi-illumination technique) as well as bile flow, serum liver enzyme activities, and tissue histomorphology.


RESULTS
In animals fed a standard diet, livers at 16 hrs after lipopolysaccharide-exposure exhibited depressed Kupffer cell phagocytic activity, enhanced hepatic microvascular leukocyte activation, leukocytic tissue infiltration, sinusoidal perfusion failure, and parenchymal cell apoptosis. Hepatic microvascular injury was further accompanied by reduced bile flow and enhanced liver enzyme release. The fish oil enriched diet did not significantly change the multiple features of endotoxemia-associated liver injury; however, it maintained arterial blood pressure, systemic leukocyte count, and acid base balance and showed a tendency toward improved survival on lipopolysaccharide exposure with a 16 hr-survival rate of 80% (p =.06 vs. survival rate of 40% in animals fed a regular diet). Moreover, slightly increased serum concentrations of interleukin-10 coincided with enhanced concentrations of interleukin-6 in fish oil fed endotoxemic animals. Healthy, non-lipopolysaccharide-exposed, fish oil fed animals did not differ from those fed with the regular diet, except for dampened Kupffer cell phagocytic activity.


CONCLUSIONS
Fish oil feeding does not protect from local endotoxemia-induced hepatic microvascular dysfunction. However, dietary modulation of inflammatory mediator response by macrophages, constituting an appropriate immune response, could add to the survival advantage seen in fish oil-fed animals on exposure to lipopolysaccharide.
Vollmar
Brigitte
B
Institute for Clinical & Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
Bauer
Claudia
C
Menger
Michael D
MD
D000136:Acid-Base Equilibrium; D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure / Q000502:physiology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications* / Q000401:mortality; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007728:Kupffer Cells / Q000502:physiology; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology; D008099:Liver / Q000098:blood supply; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D008833:Microcirculation; D010587:Phagocytosis; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000008:administration & dosage*
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D015850:Interleukin-6; D014280:Triglycerides; C077446:Pikasol; D016753:Interleukin-10