Dias 2022 Free Radic Biol Med

Dias C, Lourenço CF, Laranjinha J, Ledo A (2022) Modulation of oxidative neurometabolism in ischemia/reperfusion by nitrite. https://doi.org/10.1016/j.freeradbiomed.2022.11.021

» Free Radic Biol Med 193:779-86. PMID: 36403737 Open Access

Dias C, Lourenco CF, Laranjinha J, Ledo A (2022) Free Radic Biol Med

Abstract: Nitrite has been viewed in the past essentially as an inert metabolic endpoint of nitric oxide (^•NO). However, it has become evident that, under certain conditions, nitrite can be a source of ^•NO. In the brain, this alternative source of ^•NO production independent of nitric oxide synthase activity may be particularly relevant in ischemia/reperfusion (I/R), where low oxygen availability limits enzymatic production of ^•NO. Notably, in vivo concentration of nitrite can be easily increased with diet, through the ingestion of nitrate-rich foods, opening the window for a therapeutic intervention based on diet. Considering the modulation of mitochondrial respiration by ^•NO, we have hypothesized that the protective action of nitrite in I/R may also result from modulation of mitochondrial function. We used high-resolution respirometry to evaluate the effects of nitrite in two in vitro models of I/R. In both cases, an increase in oxygen flux was observed following reoxygenation, a phenomenon that has been coined "oxidative burst". The amplitude of this "oxidative burst" was decreased by nitrite in a concentration-dependent manner. Additionally, a pilot in vivo study in which animals received a nitrate-rich diet as a strategy to increase circulating and tissue levels of nitrite also revealed that the "oxidative burst" was decreased in the nitrate-treated animals. These results may provide mechanistic support to the observation of a protective effect of nitrite in situations of brain ischemia. • Keywords: Hippocampus, Ischemia-reperfusion, Nitric oxide, Nitrite, Oxidative burst, Respirometry • Bioblast editor: Plangger M • O2k-Network Lab: PT Coimbra Laranjinha J

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 

Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Nervous system  Preparation: Permeabilized tissue, Intact cells 

Coupling state: ROUTINE, OXPHOS, ET  Pathway: N, S, ROX  HRR: Oxygraph-2k 

2022-11