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- Title
Fish oil supplementation and essential fatty acid deficiency reduce nitric oxide synthesis by rat macrophages.
- Authors
Boutard, Valérie; Fououeray, Bruno; Philippe, Carole; Perez, Joëlle; Baud, Laurent
- Abstract
Both fish oil-derived ω-3 Polyunsaturated fatty acid (ω3 PUFA) supplementation and essential fatty acid (EFA) deficiency have been shown to exert anti-inflammalory 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-α) 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 (ω3 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 ω3 PUFA supplementation and EFA deficiency, respectively, NO2- returned to control levels two weeks after the end of diet. Macrophage production of TNF-α 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 ω3 PUFA-supplemented diet and EFA-deficient diet. Diet-induced reduction of NO synthase activity was specific for the inducible form since constitutive NO synthase activity in vascular wall was unaffected by EFA deficiency, and even significantly increased by ω3 PUFA supplementation. These data demonstrate that NO synthesis by rat macrophages is down-regulated by both ω3-PUFA supplemented diet and EFA-deficient diet. This may contribute to the explanation of the anti-inflammatory effects of such dietary treatments.
- Subjects
FISH oils; ESSENTIAL fatty acids; CYTOKINES; INFLAMMATORY mediators; IMMUNOREGULATION; TUMOR necrosis factors; MESSENGER RNA; NITRIC oxide; AMINO acids
- Publication
Kidney International, 1994, Vol 46, Issue 5, p1280
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1994.395