Modulation of oxidative neurometabolism in ischemia/reperfusion by nitrite.

Autor: Dias C; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, Coimbra, Portugal., Lourenço CF; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, Coimbra, Portugal., Laranjinha J; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, Coimbra, Portugal., Ledo A; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, Coimbra, Portugal. Electronic address: analedo@ff.uc.pt.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2022 Nov 20; Vol. 193 (Pt 2), pp. 779-786. Date of Electronic Publication: 2022 Nov 18.
DOI: 10.1016/j.freeradbiomed.2022.11.021
Abstrakt: Nitrite has been viewed essentially as an inert metabolic endpoint of nitric oxide ( • NO). However, 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.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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