Abstract Title:

Omega-3 fatty acid supplementation attenuates oxidative stress, inflammation, and tubulointerstitial fibrosis in the remnant kidney.

Abstract Source:

Am J Physiol Renal Physiol. 2009 Aug 5. PMID: 19656915

Abstract Author(s):

Won Suk An, Hyun Ju Kim, Kyu-Hyang Cho, Nosratola D Vaziri


Significant reduction of renal mass initiates a series of hemodynamic and non-hemodynamic events which lead to proteinuria, glomerulosclerosis, tubulo-interstitial injury and end-stage renal failure. Lipid mediators derived from fatty acids participate in regulation of renal hemodynamic and non-hemodynamic processes that influence progression of renal disease. Composition of cellular fatty acids and hence related signaling responses are influenced by their dietary contents. Consumption of omega-3 fatty acids (O-3FA) has proven effective in mitigating atherosclerosis. We tested the hypothesis that omega-3 fatty acid (O-3FA) supplementation may retard progression and attenuate upregulation of pathways involved in oxidative stress, inflammation and fibrosis in rats with renal mass reduction. Sprague-Dawley rats were subjected to 5/6 nephrectomy (CRF) and randomly assigned to the untreated and O-3FA-treated (0.3 g/kg/day by gastric gavage for 12 weeks) groups. Sham-operated rats served as controls. The untreated CRF rats exhibited proteinuria, hypertension, azotemia, upregulations of renal tissue NAD(P)H oxidase, MCP-1, COX-2, PAI-1, TGF-beta, Smad2, alpha-smooth muscle actin, fibronectin and hepatocyte growth factor (HGF), activation of ERK1/2 and NFkappaB, downregulation of Smad 7, intense mononuclear leukocyte infiltration, tubulo-interstitial fibrosis and glomerulosclerosis. O-3FA supplementation significantly lowered COX-2, , NAD(P)H oxidase (NOX-4, gp91(phox), p47(phox), p22(phox)), PAI-1, TGF-beta, connective tissue growth factor (CTGF), alpha-smooth muscle actin, fibronectin, Smad2 and MCP-1, raised Smad7, and attenuated, ERK1/2 and NFkappaB activation tubulo-interstitial fibrosis and inflammation. Thus long-term O-3FA supplementation can reduce or reverse up-regulation of pro-oxidant, pro- inflammatory and pro-fibrotic pathways and attenuate tubulo-interstitial fibrosis in the remnant kidney. Key words: chronic kidney disease, NAD(P)H oxidase, Smad, TGF-beta.

Study Type : Animal Study

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Sayer Ji
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