Dietary nitrate attenuates renal ischemia-reperfusion injuries by modulation of immune responses and reduction of oxidative stress.

Autor:	Yang T; Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Dept. of Medicine, Div. of Nephrology (T.Y.), Dept. of Anesthesiology (N.T.), Duke University Medical Center, Durham, NC, USA. Electronic address: ting.yang2@duke.edu., Zhang XM; Dept. of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden., Tarnawski L; Dept. of Medicine, Center for Molecular Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Peleli M; Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Zhuge Z; Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Terrando N; Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Dept. of Medicine, Div. of Nephrology (T.Y.), Dept. of Anesthesiology (N.T.), Duke University Medical Center, Durham, NC, USA., Harris RA; Dept. of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden., Olofsson PS; Dept. of Medicine, Center for Molecular Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Larsson E; Dept. of Immunology, Genetics and Pathology, Uppsala University, Sweden., Persson AEG; Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Dept. of Medical Cell Biology, Uppsala University, Sweden., Lundberg JO; Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Weitzberg E; Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Carlstrom M; Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. Electronic address: mattias.carlstrom@ki.se.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2017 Oct; Vol. 13, pp. 320-330. Date of Electronic Publication: 2017 Jun 09.
DOI:	10.1016/j.redox.2017.06.002
Abstrakt:	Ischemia-reperfusion (IR) injury involves complex pathological processes in which reduction of nitric oxide (NO) bioavailability is suggested as a key factor. Inorganic nitrate can form NO in vivo via NO synthase-independent pathways and may thus provide beneficial effects during IR. Herein we evaluated the effects of dietary nitrate supplementation in a renal IR model. Male mice (C57BL/6J) were fed nitrate-supplemented chow (1.0mmol/kg/day) or standard chow for two weeks prior to 30min ischemia and during the reperfusion period. Unilateral renal IR caused profound tubular and glomerular damage in the ischemic kidney. Renal function, assessed by plasma creatinine levels, glomerular filtration rate and renal plasma flow, was also impaired after IR. All these pathologies were significantly improved by nitrate. Mechanistically, nitrate treatment reduced renal superoxide generation, pro-inflammatory cytokines (IL-1β, IL-6 and IL-12 p70) and macrophage infiltration in the kidney. Moreover, nitrate reduced mRNA expression of pro-inflammatory cytokines and chemo attractors, while increasing anti-inflammatory cytokines in the injured kidney. In another cohort of mice, two weeks of nitrate supplementation lowered superoxide generation and IL-6 expression in bone marrow-derived macrophages. Our study demonstrates protective effect of dietary nitrate in renal IR injury that may be mediated via modulation of oxidative stress and inflammatory responses. These novel findings suggest that nitrate supplementation deserve further exploration as a potential treatment in patients at high risk of renal IR injury. (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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