ArticleScientific reports2022
Zinc chelator treatment in crush syndrome model mice attenuates ischemia-reperfusion-induced muscle injury due to suppressing of neutrophil infiltration.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 11 citations in OpenAlex.
- Immune Cell Dysregulation in Hindlimb Unloading Mouse Model: Implications for Space Applications.Journal of biomedical physics & engineering · 2026Article
- Low-intensity pulsed ultrasound mitigates acute extremity compartment syndrome by mediating ferroptosis suppression.iScience · 2026Article
- Transcatheter Intra-Arterial Delivery of a Platelet-Derived Extracellular Vesicle-Enriched Preparation for Attenuating Skeletal Muscle Ischaemia-Reperfusion Injury in a Rodent Forelimb Model.Journal of extracellular vesicles · 2026Article
- Dynamic muscle damage monitoring in pig crush injury: T2-weighted Dixon and 2D ultrasound applications.Frontiers in veterinary science · 2026Article
- Impaired Antiviral and Type 3 Immune Responses in Crush Injury Patients With Earthquake-Related Trauma.Journal of immunology research · 2026Article
- A nomogram for predicting ischaemic muscle sequelae after revascularization in patients with traumatic femoral-popliteal artery injuries: a retrospective cohort study.International orthopaedics · 2025Article
- Zinc deficiency as possible link between immunosenescence and age-related diseases.Immunity & ageing : I & A · 2025Review
- Total and Free Zinc Dynamics as Biomarkers for Neurological Impairment in Traumatic Spinal Cord Injury.Nutrients · 2025Article
- Skeletal Muscle Damage and Inflammation.Advances in experimental medicine and biology · 2025Review
- Mortality risk factors for crush syndrome after an earthquake in Türkiye: Do systemic inflammatory parameters play any role?Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES · 2024Article
- Crush syndrome: a review for prehospital providers and emergency clinicians.Journal of translational medicine · 2023Review
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In crush syndrome, massive muscle breakdown resulting from ischemia-reperfusion muscle injury can be a life-threatening condition that requires urgent treatment. Blood reperfusion into the ischemic muscle triggers an immediate inflammatory response, and neutrophils are the first to infiltrate and exacerbate the muscle damage. Since free zinc ion play a critical role in the immune system and the function of neutrophils is impaired by zinc depletion, we hypothesized that the administration of a zinc chelator would be effective for suppressing the inflammatory reaction at the site of ischemia-reperfusion injury and for improving of the pathology of crush syndrome. A crush syndrome model was created by using a rubber tourniquet to compress the bilateral hind limbs of mice at 8 weeks. A zinc chelator N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) was administered immediately after reperfusion in order to assess the anti-inflammatory effect of the chelator for neutrophils. Histopathological evaluation showed significantly less muscle breakdown and fewer neutrophil infiltration in TPEN administration group compared with control group. In addition, the expression levels of inflammatory cytokine and chemokine such as IL-6, TNFα, CXCL1, CXCL2, CXCR2, CCL2 in ischemia-reperfusion injured muscle were significantly suppressed with TPEN treatment. Less dilatation of renal tubules in histological evaluation in renal tissue and significantly better survival rate were demonstrated in TPEN treatment for ischemia-reperfusion injury in crush syndrome. The findings of our study suggest that zinc chelators contributed to the resolution of exacerbation of the inflammatory response and attenuation of muscle breakdown in the acute phase after crush syndrome. In addition, our strategy of attenuation of the acute inflammatory reaction by zinc chelators may provide a promising therapeutic strategy not only for crush syndrome, but also for other diseases driven by inflammatory reactions.
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