Fish oil supplementation and essential fatty acid deficiency reduce nitric oxide synthesis by rat macrophages.
Both fish oil-derived omega-3 polyunsaturated fatty acid (omega 3 PUFA) supplementation and essential fatty acid (EFA) deficiency have been shown to exert anti-inflammatory effects and, hence, to ameliorate immune-mediated glomerulonephritis. The mechanisms underlying these effects include alterations in the production of eicosanoids, cytokines (that is, tumor necrosis factor, TNF-alpha) and reactive oxygen species by blood borne cells. Because, in addition to these mediators nitric oxide (NO) is also implicated in glomerular injury, we have examined if both diets affected macrophage NO production as well. Rats were fed a standard chow, an omega 3 PUFA-supplemented diet, or an EFA-deficient diet for six weeks before resident peritoneal macrophages were isolated. These cells were exposed to lipopolysaccharide (LPS) and the NO metabolite, nitrite (NO2-), was measured in the medium using the Griess reagent. Release of NO2- was enhanced by LPS in a dose-dependent manner. With 10 ng/ml LPS challenge, NO2- release was reduced by 37% and 57% by omega 3 PUFA supplementation and EFA deficiency, respectively. NO2- returned to control levels two weeks after the end of diet. Macrophage production of TNF-alpha responded in a similar manner. Diet-induced reduction of NO2- release was neither attributable to a reduction of inducible NO synthase mRNA levels as shown by Northern blot analysis, nor to an increased competition of NO synthase and arginase for the substrate (L-arginine). Indeed, arginase activity of macrophages was even slightly reduced by both omega 3 PUFA-supplemented diet and EFA-deficient diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Boutard
V
V
Institut National de la Santé et de la Recherche Médicale, Unité 64, Hôpital Tenon, Paris, France.
Fouqueray
B
B
Philippe
C
C
Perez
J
J
Baud
L
L
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004790:Enzyme Induction; D005228:Fatty Acids, Essential / Q000172:deficiency*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D005228:Fatty Acids, Essential; D015525:Fatty Acids, Omega-3; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases