title: Nitrate/Nitrite as Critical Mediators to Limit Oxidative Injury and Inflammation.
abstract: CONCLUSIONS
  Nitric oxide (NO) is a critical signaling molecule marked by complex chemistry and varied biological responses depending on the context of the redox environment. In the setting of inflammation, NO can not only contribute to tissue injury and be causative of oxidative damage but can also signal as an adaptive molecule to limit inflammatory signaling in multiple cell types and tissues.
  
  
  BACKGROUND
  An advance in our understanding of NO biology was the recognition of the nitrate-nitrite-NO axis, whereby nitrate (predominantly from dietary sources) could be converted to nitrite and nitrite could be reduced to NO.
  
  
  RESULTS
  Intriguingly, the recognition of multiple enzymes that serve as nitrite reductases in the setting of hypoxia or ischemia established the concept of nitrite as a circulating endocrine reservoir of NO, with the selective release of NO at sites that were primed for this reaction. This review highlights the anti-inflammatory roles of nitrite in numerous clinical conditions, including ischemia/reperfusion, transplant, cardiac arrest, and vascular injury, and in gastrointestinal inflammation.
  
  
  CONCLUSIONS
  These preclinical and clinical investigations set up further clinical trials and studies that elucidate the endogenous role this pathway plays in protection against inflammatory signaling.
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Paul
authors.initials: P
authors.lastname: Waltz
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Escobar
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Botero
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 The Center for Critical Care Nephrology, University of Pittsburgh , Pittsburgh, Pennsylvania.|3 Vascular Medicine Institute, University of Pittsburgh , Pittsburgh, Pennsylvania.|4 VA Pittsburgh Healthcare System , Pittsburgh, Pennsylvania.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Zuckerbraun
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009572:Nitrite Reductases / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D009572:Nitrite Reductases