Nitrate/Nitrite as Critical Mediators to Limit Oxidative Injury and Inflammation
Open accessAbstract
Significance: 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. Recent Advances: 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. Critical Issues: 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. Future Directions: 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. Antioxid. Redox Signal. 23, 328–339.
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In the stomach, nitrite is partially reduced to NO and other reactive nitrogen species in a non-enzymatic process, contributing to antimicrobial defences and regulation of gastric blood flow.
“After being swallowed, nitrite enters the acidic environment of the stomach, where it is partially reduced to NO and other reactive nitrogen species in a non-enzymatic process. This contributes to the body’s antimicrobial defences and the regulation of gastric blood flow.”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [34]
Remaining nitrite is absorbed into the bloodstream and acts as a systemic NO reservoir, particularly in hypoxic and acidic conditions.
“The remaining nitrite is absorbed into the bloodstream and acts as a systemic NO reservoir, particularly in hypoxic and acidic conditions [34].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [34]
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Effect on health from consumption of meat and meat products
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“The remaining nitrite is absorbed into the bloodstream and acts as a systemic NO reservoir, particularly in hypoxic and acidic conditions [34].”
- Authors
- Waltz, P., Escobar, D., Botero, A. M., & Zuckerbraun, B. S.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Zuckerbraun, Brian S.
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2015-08
- Volume
- 23
- Issue
- 4
- Pages
- 328-339
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC4692126
- OpenAlex
- W1444897672
- Cited by
- 70
- References
- 31
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 11 · 2023: 12 · 2022: 2 · 2021: 8 · 2020: 8 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 1
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM082830)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- nitric oxide, nitrite, nitrite reductase, oxidative damage, inflammation, ischemia-reperfusion injury, transplantation, cardiac arrest, vascular injury, gastrointestinal inflammation, hypoxia, redox signaling
- MeSH terms
- Animals, Humans, Inflammation, Nitrates, Nitric Oxide, Nitrite Reductases, Nitrites, Oxidation-Reduction, Signal Transduction, Reactive Oxygen Species
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