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2017 ; 13
(ä): 320-330
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Dietary nitrate attenuates renal ischemia-reperfusion injuries by modulation of
immune responses and reduction of oxidative stress
#MMPMID28623824
Yang T
; Zhang XM
; Tarnawski L
; Peleli M
; Zhuge Z
; Terrando N
; Harris RA
; Olofsson PS
; Larsson E
; Persson AEG
; Lundberg JO
; Weitzberg E
; Carlstrom M
Redox Biol
2017[Oct]; 13
(ä): 320-330
PMID28623824
show ga
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-1?, 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.
|*Oxidative Stress
[MESH]
|Acute Kidney Injury/*drug therapy
[MESH]
|Animals
[MESH]
|Cells, Cultured
[MESH]
|Dietary Supplements
[MESH]
|Interleukin-6/genetics/*metabolism
[MESH]
|Kidney/blood supply
[MESH]
|Macrophage Activation
[MESH]
|Macrophages/*drug effects/immunology
[MESH]
|Male
[MESH]
|Mice
[MESH]
|Mice, Inbred C57BL
[MESH]
|Nitrates/administration & dosage/pharmacology/*therapeutic use
[MESH]