ArticleBlood advances2020
Mn porphyrins as a novel treatment targeting sickle cell NOXs to reverse and prevent acute vaso-occlusion in vivo.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Exercise modulates redox homeostasis in cardiovascular and metabolic diseases: from bench to clinic.Cardiovascular diabetology · 2026Review
- Protein Arginine Methyltransferases in γ-Globin Regulation and Sickle Cell Disease: Emerging Connections to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- Redox Regulation of Microvascular Physiology and Pathophysiology: Insights into Therapeutic Strategies and Limitations.Antioxidants & redox signaling · 2025Review
- Article
- Rpl13a snoRNAs-regulated NADPH oxidase 1-dependent ROS generation: A novel RBC pathway mediating complement C3a deposition and triggering thrombosis in aging and venous blood clotting disorders.Free radical biology & medicine · 2025Article
- Red blood cell Rpl13a small noncoding nucleolar RNAs guides 2'-O-methylation on peroxidasin messenger RNA promoting venous thrombosis in aging.Journal of thrombosis and haemostasis : JTH · 2025Article
- MnSOD Mimetics in Therapy: Exploring Their Role in Combating Oxidative Stress-Related Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Analysis of structural effects of sickle cell disease on brain vasculature of mice using three-dimensional quantitative phase imaging.Journal of biomedical optics · 2023Article
- Keap1-Nrf2 Heterodimer: A Therapeutic Target to Ameliorate Sickle Cell Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Manganese-Based Nanotheranostics for Magnetic Resonance Imaging-Mediated Precise Cancer Management.International journal of nanomedicine · 2023Review
- Erythrocyte oxidative stress and thrombosis.Expert reviews in molecular medicine · 2022Review
- The oral ferroportin inhibitor vamifeport improves hemodynamics in a mouse model of sickle cell disease.Blood · 2022Article
- Sympathoinhibition and Vasodilation Contribute to the Acute Hypotensive Response of the Superoxide Dismutase Mimic, MnTnBuOE-2-PyPAdvances in redox research · 2021Article
- The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications.Antioxidants (Basel, Switzerland) · 2021Review
- Sickle cell vaso-occlusion: The dialectic between red cells and white cells.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Pyridoxamine: another vitamin for sickle cell disease?Haematologica · 2020Article
- Post-translational modification as a response to cellular stress induced by hemoglobin oxidation in sickle cell disease.Scientific reports · 2020Article
- Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs in Venous Thrombosis.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In sickle cell disease (SCD), adhesion of sickle red blood cells (SSRBCs) and activated leukocytes in inflamed venules affects blood rheology, causing vaso-occlusive manifestations and vital reduction in microvascular blood flow. Recently, we found that NADPH oxidases (NOXs) create a vicious feedback loop within SSRBCs. This positive feedback loop mediates SSRBC adhesion to the endothelium. We show for the first time the therapeutic effectiveness of the redox-active manganese (Mn) porphyrins MnTnBuOE-2-PyP5+ (MnBuOE; BMX-001) and MnTE-2-PyP5+ (MnE; BMX-010, AEOL10113) to treat established vaso-occlusion in a humanized sickle mouse model of an acute vaso-occlusive crisis using intravital microscopy. These Mn porphyrins can suppress SSRBC NOX activity. Subcutaneous administration of only 1 dose of MnBuOE or MnE at 0.1 to 2 mg/kg after the inflammatory trigger of vaso-occlusion, or simultaneously, reversed and reduced leukocyte and SSRBC adhesion, diminished leukocyte rolling, restored blood flow, and increased survival rate. Furthermore, MnBuOE and MnE administered to sickle mice subcutaneously at 0.1 to 1 mg/kg for 28 days (except on weekends) did not exacerbate anemia, which seemed to be due to downregulation of both SSRBC reactive oxygen species production and exposure of the eryptotic marker phosphatidylserine. In addition, Mn porphyrins ameliorated leukocytosis, venous blood gases, endothelial activation, and organ oxidative damage. Our data suggest that Mn porphyrins, likely by repressing NOX-mediated adhesive function of SSRBCs and activated leukocytes, could represent a novel, safe therapeutic intervention to treat or prevent the establishment of acute pain crises. These NOX-targeted antioxidants merit further assessment in SCD clinical trials.
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