Effects of nitrite on modulating ROS generation following ischemia and reperfusion

It has long been known that the generation of reactive oxygen species (ROS) is a major cause of injury after ischemia/reperfusion. More recently it has emerged that the predominant source of these ROS are the mitochondria, which are specifically damaged during prolonged ischemic episodes. Several st...

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Bibliographic Details
Published in:Advanced drug delivery reviews 2009-04, Vol.61 (4), p.339-350
Main Authors: Raat, N.J.H., Shiva, S., Gladwin, M.T.
Format: Article
Language:English
Subjects:
Animals
Cell protection
Humans
Ischemia
Ischemia - metabolism
Ischemia - prevention & control
Nitric Oxide Donors - pharmacology
Nitric Oxide Donors - therapeutic use
Nitrite
Nitrites - metabolism
Nitrites - pharmacology
Reactive Oxygen Species - antagonists & inhibitors
Reactive Oxygen Species - metabolism
Reperfusion
Reperfusion Injury - metabolism
Reperfusion Injury - prevention & control
ROS
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Summary:It has long been known that the generation of reactive oxygen species (ROS) is a major cause of injury after ischemia/reperfusion. More recently it has emerged that the predominant source of these ROS are the mitochondria, which are specifically damaged during prolonged ischemic episodes. Several strategies have been tested to attenuate mitochondrial damage and reperfusion ROS. Most successful has been ischemic preconditioning, a procedure in which repetitive short periods of ischemia and reperfusion reduce injury from a subsequent prolonged ischemia and reperfusion. Recently, ischemic postconditioning, whereby reperfusion after prolonged ischemia is repetitively interrupted for a short period, has also been shown to equally protect as ischemic preconditioning. Both procedures activate the same down-stream kinase pathways that minimize apoptosis and tissue damage. Endothelial nitric oxide synthase is a target of these kinase pathways and nitric oxide (NO) administration can mimic its protective effect. However, the optimal NO dose is difficult to determine and excess NO levels have been shown to be detrimental. A recently described physiological storage pool of NO, nitrite, has been shown to be a potent mediator of cytoprotection after ischemia/reperfusion that mechanistically reduces mitochondrial ROS generation at reperfusion. Here, we describe the sources, bioactivaton, and mechanisms of action of nitrite and discuss the potential of this simple anion as a therapeutic to protect against ischemia/reperfusion injury.
ISSN:0169-409X
1872-8294
DOI:10.1016/j.addr.2009.02.002