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Dietary nitrate attenuates renal ischemia-reperfusion injuries by modulation of immune responses and reduction of oxidative stress
Karolinska Inst, Dept Physiol & Pharmacol, Nanna Svartz Vag 2, S-17177 Stockholm, Sweden.;Duke Univ, Med Ctr, Dept Med, Div Nephrol, Durham, NC 27710 USA..
Karolinska Univ Hosp Solna, Ctr Mol Med, Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med, Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, Nanna Svartz Vag 2, S-17177 Stockholm, Sweden..
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2017 (English)In: Redox Biology, ISSN 0090-7324, E-ISSN 2213-2317, Vol. 13, p. 320-330Article in journal (Refereed) Published
Abstract [en]

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 (1.0 mmol/kg/day) or standard chow for two weeks prior to 30 min 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-1 beta, 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.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV , 2017. Vol. 13, p. 320-330
Keywords [en]
Acute kidney injury, Inflammation, Inorganic nitrate, NADPH oxidase, Nitric oxide, Oxidative stress
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-335128DOI: 10.1016/j.redox.2017.06.002ISI: 000410470000025PubMedID: 28623824OAI: oai:DiVA.org:uu-335128DiVA, id: diva2:1162360
Funder
Swedish Heart Lung Foundation, 20140448Swedish Research Council, 2016-01381The Karolinska Institutet's Research Foundation, 2415/2012-225, 2-3707/2013Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2017-12-04Bibliographically approved

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