ArticlePloS one2019
Batroxobin accelerated tissue repair via neutrophil extracellular trap regulation and defibrinogenation in a murine ischemic hindlimb model.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Targeting neutrophil extracellular traps: A novel strategy for treating heterotopic ossification.World journal of orthopedics · 2025Article
- Effects of Exercise on Cardiovascular and Metabolic Responses in Adults and Childhood Cancer Survivors: The Role of NETosis and Low-Grade Inflammation as a Novel Therapeutic Target-A Narrative Review.International journal of molecular sciences · 2025Review
- Efficacy of Batroxobin on Ischemia-Reperfusion Injury in Epigastric Artery Island Flaps in Rats.Plastic and reconstructive surgery. Global open · 2025Article
- Acute myocardial infarction after batroxobin treatment of sudden sensorineural hearing loss: Case report.Medicine · 2025Article
- Targets Involved in the Pharmacology of Bothrops Snakebite:Current drug targets · 2025Review
- Thromboinflammatory complications ofFrontiers in immunology · 2025Review
- Neutrophil extracellular traps in ischemic stroke: mechanisms, clinical implications, and therapeutic potential.Frontiers in neurology · 2025Review
- From inflammation to bone formation: the intricate role of neutrophils in skeletal muscle injury and traumatic heterotopic ossification.Experimental & molecular medicine · 2024Review
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- A Metalloproteinase Cocktail from the Venom ofToxins · 2023Article
- [Management strategy of femoral artery pseudoaneurysm combined with infectious wounds].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2023Observational
- Immunomodulation for Tissue Repair and Regeneration.Tissue engineering and regenerative medicine · 2023Review
- Clinical Profiles and Prognoses of Adult Patients with Full-Frequency Sudden Sensorineural Hearing Loss in Combination Therapy.Journal of clinical medicine · 2023Article
- Inflammatory myopathies and beyond: The dual role of neutrophils in muscle damage and regeneration.Frontiers in immunology · 2023Review
- Human Transcriptome Array Analysis Identifies CDR2 as a Novel Suppressed Gene for Kawasaki Disease.Diagnostics (Basel, Switzerland) · 2022Article
- The chemistry of snake venom and its medicinal potential.Nature reviews. Chemistry · 2022Review
- Review
- Review
- Neutrophil Extracellular Traps: A New Player in Cancer Metastasis and Therapeutic Target.Journal of experimental & clinical cancer research : CR · 2021Review
- Use of Batroxobin in Central and Peripheral Ischemic Vascular Diseases: A Systematic Review.Frontiers in neurology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Batroxobin, isolated from Bothrops moojeni, is a defibrinogenating agent used as a thrombin-like serine protease against fibrinogen for improving microcirculation. Here, we investigated whether, and if so, how batroxobin restores ischemic tissue injury in terms of anti-inflammatory effects. In an in vitro flow cytometry assay for human neutrophil extracellular traps (NETs), batroxobin (DF-521; Defibrase) inhibited human NETs induced by tumor necrosis factor-α (TNF-α) in the presence of human fibrinogen. Next, the effect of batroxobin was investigated by immunohistochemistry of the anterior tibial muscle (ATM) in an ischemic hindlimb model using C57BL/6J mice intraperitoneally injected with DF-521 versus the saline control. NETs and fibrinogen deposition in the ischemic ATM decreased in DF-521-treated mice on day 2 after ischemia. Meanwhile, reverse transcription-quantitative PCR assay of the ischemic ATM unveiled continuous downregulation in the expression of the genes; Tnf-α and nitric oxide synthase2 (Nos2) with hypoxia-inducible factor-1α (Hif-1α) and vascular endothelial growth factor-a (Vegf-a) from day 3 to day 7, but the upregulation of arginase-1 (Arg-1) and placental growth factor (Plgf) with myogenin (Myog) on day 7. Daily intraperitoneal DF-521 injection for the initial 7 days into mice with ischemic hindlimbs promoted angiogenesis and arteriogenesis on day 14. Moreover, DF-521 injection accelerated myofiber maturation after day 14. Laser doppler imaging analysis revealed that blood perfusion in DF-521-injected mice significantly improved on day 14 versus the saline control. Thus, DF-521 improves microcirculation by protecting NETs with tissue defibrinogenation, thereby protecting against severe ischemic tissue injury and accelerating vascular and skeletal muscular regeneration. To our knowledge, batroxobin might be the first clinically applicable NET inhibitor against ischemic diseases.
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