title: Effects of eicosapentaenoic acid on the early stage of type 2 diabetic nephropathy in KKA(y)/Ta mice: involvement of anti-inflammation and antioxidative stress.
abstract: Eicosapentaenoic acid (EPA) has been reported to have beneficial effects on the progression of various renal diseases including diabetic nephropathy; however, the precise mechanisms are not completely understood. We examined the effects of EPA on the early stage of type 2 diabetic nephropathy in KKA(y)/Ta mice and the possible role of inflammation, oxidative stress, and growth factor in this process. KKA(y)/Ta mice were divided into 2 groups. The treatment group was injected with EPA ethyl ester at 1 g/kg per day intraperitoneally from 12 to 20 weeks of age and the control group was injected with saline. Renal morphologic examinations were performed after 8 weeks of treatment. Glomerular macrophage infiltration and expression of monocyte chemoattractant protein 1, malondialdehyde (MDA), nitrotyrosine, transforming growth factor beta1 (TGF-beta1), and type I collagen were evaluated. Eicosapentaenoic acid decreased the levels of urinary albumin, serum triglyceride and MDA, and improved glucose intolerance in KKA(y)/Ta mice. Morphometric analysis showed that accumulation of extracellular matrix and the tubulointerstitial fibrosis area were significantly decreased after treatment. Immunohistochemistry revealed that glomerular macrophage infiltration and the expression of MDA and nitrotyrosine in KKA(y)/Ta mice were increased and were inhibited by EPA treatment. Protein and gene expression levels of monocyte chemoattractant protein 1, TGF-beta1, and type I collagen, which were evaluated by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction, were down-regulated in the EPA treatment group. In conclusion, EPA improves type 2 diabetic nephropathy in KKA(y)/Ta mice. This beneficial effect might be mediated by attenuation of metabolic abnormalities and inhibition of renal inflammation, oxidative stress, and TGF-beta expression.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Minfang
authors.initials: M
authors.lastname: Zhang
authors.forename: Shinji
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Masukazu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Leyi
authors.initials: L
authors.lastname: Gu
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakamura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kaneko
authors.forename: Tomohito
authors.initials: T
authors.lastname: Gohda
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Qian
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horikoshi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000032:analysis; D024042:Collagen Type I / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010641:Phenotype; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D024042:Collagen Type I; D053773:Transforming Growth Factor beta1; C002744:3-nitrotyrosine; D014443:Tyrosine; D015118:Eicosapentaenoic Acid