A dietary conjugated linoleic acid treatment that slows renal disease progression alters renal cyclooxygenase-2-derived prostanoids in the Han: SPRD-cy rat

被引:17
作者
Wakefield, Andrew P. [1 ]
Ogborn, Malcolm R. [1 ,2 ]
Ibrahim, Naser [1 ]
Aukema, Harold M. [1 ]
机构
[1] Univ Manitoba, Dept Human Nutr Sci, Winnipeg, MB R2H 2A6, Canada
[2] Univ No British Columbia, No Med Program, Prince George, BC V2K 4Z9, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
Conjugated linoleic acid; Kidney disease; Prostanoid; Cyclooxygenase; 2; Phospholipase A(2); PROSTAGLANDIN E-2; ENDOTHELIAL-CELLS; COX-2; EXPRESSION; NITRIC-OXIDE; INHIBITION; KIDNEY; INJURY; PGE(2); MOUSE; BIOSYNTHESIS;
D O I
10.1016/j.jnutbio.2011.04.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A mixture of dietary conjugated linoleic acid (CLA) isomers reduces inflammation and mitigates disease progression in the Han:SPRD-cy rat model of chronic kidney disease. Since cyclooxygenase (COX) activities and prostanoid levels are higher in diseased kidneys in this rat, and dietary CLA can inhibit COX2 and prostanoid production in other tissues, the effects of dietary CLA were investigated. Kidney homogenates from normal and diseased Han:SPRD-cy rats were analyzed for prostanoid levels under various conditions: endogenous levels, steady-state levels (60-min incubations) and produced by COX isoforms. Thromboxane B-2 (TXB2; TXA(2) metabolite), 6-keto-prostaglandin F-1 alpha (6-keto-PGF(1 alpha); PGI(2) metabolite) and PGE(2) levels under these conditions were two- to ninefold higher in diseased kidneys. Dietary CLA resulted in similar to 32%-53% lower levels of prostanoids produced by total COX and COX2 activities in normal and diseased kidneys and partially mitigated alterations in COX2 protein levels associated with disease. The COX1 protein and activity were higher in renal disease, resulting in increased production of TXB2 and 6-ketoPGF(1 alpha), but not PGE(2). Dietary CLA had no effect on COX1. however. Disease resulted in up to twofold higher ratios of TXB2/6-ketoPGF(1 alpha), TXB2/PGE(2) and 6-ketoPGF(1 alpha)/PGE(2), and dietary CLA partially mitigated these increases under several conditions. Elevated levels of renal membrane associated cytosolic phospholipase A(2) in diseased kidneys also were reduced by 50% with CLA feeding. The effects of CLA feeding on COX2 protein levels and activity indicate that the beneficial effect of dietary CLA in this renal disorder is mediated in part via effects on COX2-derived prostanoids. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:908 / 914
页数:7
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