title: Omega-3 fatty acid supplementation attenuates oxidative stress, inflammation, and tubulointerstitial fibrosis in the remnant kidney.
abstract: 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-beta, Smad2, alpha-smooth muscle actin, fibronectin, and hepatocyte growth factor, activation of ERK1/2 and NF-kappaB, 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-beta, connective tissue growth factor, alpha-smooth muscle actin, fibronectin, Smad2, and MCP-1, raised Smad7, and attenuated ERK1/2 and NF-kappaB 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.
authors: Div. of Nephrology and Hypertension, UCI Medical Center, 101 The City Drive, Bldg. 53, Rm. 125, Rt. 81, Orange, CA 92868, USA.
authors: Won Suk
authors: WS
authors: An
authors: Hyun Ju
authors: HJ
authors: Kim
authors: Kyu-Hyang
authors: KH
authors: Cho
authors: Nosratola D
authors: ND
authors: Vaziri
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019587:Dietary Supplements; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000517:prevention & control; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control*; D007668:Kidney / Q000473:pathology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009393:Nephritis / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051899:Smad2 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D018932:Chemokine CCL2; D055513:Connective Tissue Growth Factor; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D015525:Fatty Acids, Omega-3; D005353:Fibronectins; D017228:Hepatocyte Growth Factor; D019255:NADPH Oxidases; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D051899:Smad2 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; C491766:Ccl2 protein, rat; C497784:Smad2 protein, rat; C497808:Smad7 protein, rat; C498862:Acta2 protein, rat; C489691:Ptgs2 protein, rat