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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/F895    most recent 00217.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by An, W. S. Articles by Vaziri, N. D. PubMed PubMed Citation Articles by An, W. S. Articles by Vaziri, N. D.

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

¹Division of Nephrology and Hypertension, University of California, Irvine, California; ; ²Department of Internal Medicine, Dong-A University, Busan; and ; ³Department of Internal Medicine, Yeungnam University, Daegu, Republic of Korea

Submitted April 17, 2009 ; accepted in final form August 4, 2009

Significant reduction of renal mass initiates a series of hemodynamic and nonhemodynamic events which lead to proteinuria, glomerulosclerosis, tubulointerstitial injury, and end-stage renal failure. Lipid mediators derived from fatty acids participate in regulation of renal hemodynamic and nonhemodynamic 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 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 [chronic renal failure (CRF)] and randomly assigned to the untreated and O-3FA-treated (0.3 g·kg^–1·day^–1 by gastric gavage for 12 wk) 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-β, Smad2, -smooth muscle actin, fibronectin, and hepatocyte growth factor, activation of ERK1/2 and NF-B, downregulation of Smad7, intense mononuclear leukocyte infiltration, tubulointerstitial 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-β, connective tissue growth factor, -smooth muscle actin, fibronectin, Smad2, and MCP-1, raised Smad7, and attenuated ERK1/2 and NF-B activation, tubulointerstitial fibrosis, and inflammation. Thus, long-term O-3FA supplementation can reduce or reverse upregulation of prooxidant, proinflammatory, and profibrotic pathways and attenuate tubulointerstitial fibrosis in the remnant kidney.

chronic kidney disease; NAD(P)H oxidase; TGF-β; Smad; epithelial-mesenchymal transition; MAP Kinase