Nitrite reduces ischemia/reperfusion-induced muscle damage and improves survival rates in rat crush injury model
Abstract
BACKGROUND: Nitrite is an intrinsic signaling molecule with potential therapeutic implications in mammalian ischemia/reperfusion (I/R) injury of the heart, liver, and kidney. Although limb muscle compression and subsequent reperfusion are the causative factors in developing crush syndrome (CS), there has been no report evaluating the therapeutic effects of nitrite on CS. We therefore tested whether nitrite could be a therapeutic agent for the treatment of CS. METHODS: To create a CS model, anesthetized rats were subjected to bilateral hind limb compression with rubber tourniquets for 5 hours, followed by reperfusion for 0 hour to 6 hours while monitoring blood pressure. Saline for the CS group or sodium nitrite (NaNO(2)-100, 200, and 500 μmol/kg) for the nitrite-treated CS groups was intravenously administered immediately before reperfusion. Blood and tissue samples were collected for biochemical analysis. RESULTS: Tissue nitrite levels in injured muscles were significantly reduced in the CS group compared with the sham group during I/R injury. Nitrite administration to CS rats restored nitric oxide bioavailability by enhancing nitrite levels of the muscle, resulting in a reduction of rhabdomyolysis markers such as potassium, lactate dehydrogenase, and creatine phosphokinase. Nitrite treatment also reduced plasma levels of interleukin-6 and myeloperoxidase activities in muscle and lung tissues, finally resulting in a dose-dependent improvement of survival rate from 24% (CS group) to 36% (NaNO(2)-100 group) and 64% (NaNO(2)-200 and 500 groups). CONCLUSION: These results indicate that nitrite reduces I/R-induced muscle damage through its cytoprotective action and contributes to improved survival rate in a rat CS model.
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Vascular NO availability is expected to be impaired due to reduced NOS activity in ischemia and subsequent consumption by superoxide during reperfusion, resulting in severe ischemia/reperfusion injury.
“The availability of vascular NO would thus be expected to be impaired due to the reduced NOS activity in ischemia and subsequent consumption by superoxide during reperfusion [95], resulting in severe ischemia/reperfusion injury [30].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [95]
Sodium nitrite decreases plasma IL-6 concentrations and increases survival rate in a crush injury model in rats.
“sodium nitrite decreases plasma IL-6 concentrations and increases survival rate in a crush injury model in rats (134)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [134]
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- Authors
- Murata, I., Nozaki, R., Ooi, K., Ohtake, K., Kimura, S., Ueda, H., Nakano, G., Sonoda, K., Inoue, Y., Uchida, H., Kanamoto, I., Morimoto, Y., & Kobayashi, J.
- Affiliations
- Kinjo Gakuin University (JP)
- Venue
- Journal of Trauma and Acute Care Surgery
- Published
- 2012-06
- Volume
- 72
- Issue
- 6
- Pages
- 1548-1554
- ISSN
- 2163-0755 (ISSN-L)
- OpenAlex
- W1977155874
- Cited by
- 33
- References
- 22
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 6 · 2016: 2 · 2015: 4 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Trauma: Injury, Infection, and Critical Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22592021)
- Topics
- Health Sciences › Medicine › Surgery › Muscle and Compartmental Disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- nitrite, crush syndrome, ischemia-reperfusion injury, muscle damage, sodium nitrite, nitric oxide bioavailability, rhabdomyolysis, interleukin-6, myeloperoxidase, survival rate, cytoprotection
- MeSH terms
- Analysis of Variance, Animals, Blood Pressure Determination, Crush Syndrome, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Hemodynamics, Hindlimb, Male, Peroxidase, Nitrites, Random Allocation, Reference Values, Rhabdomyolysis, Risk Factors, Reperfusion Injury, Interleukin-6, Survival Analysis, Treatment Outcome, Rats, Wistar, Muscle, Skeletal, Rats, Kaplan-Meier Estimate
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