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Updated: Aug 11, 2026
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Analytical Techniques for Assaying Nitric Oxide Bioactivity
Published on: June 18, 2012
Iron chelates bind nitric oxide and decrease mortality in an experimental model of septic shock
W M Kazmierski1, G Wolberg, J G Wilson
1Division of Organic Chemistry, Burroughs Wellcome, Research Triangle Park, NC 27709, USA.
Summary
Iron chelators ferrioxamine B and DTPA protect against septic shock. The iron-free ligand H4DFB+ was more effective, suggesting NO scavenging and redox catalysis are key mechanisms for novel drug development.
Area of Science:
- Biochemistry
- Pharmacology
- Medicinal Chemistry
Background:
- Septic shock is a life-threatening condition often exacerbated by dysregulated nitric oxide (NO) production.
- Iron chelators are being investigated for their therapeutic potential in various diseases, including sepsis.
Purpose of the Study:
- To evaluate the efficacy of ferrioxamine B [FeIII(HDFB)+] and diethylenetri-aminepentaacetic acid [FeIII(DTPA)2-] in protecting against septic shock.
- To investigate the underlying mechanisms of protection, focusing on NO scavenging and redox catalysis.
Main Methods:
- Mice were subjected to septic shock induced by Corynebacterium parvum and lipopolysaccharide.
- Treatment efficacy was assessed using iron complexes and iron-free ligands.
- Electrochemical studies were performed to analyze the interaction of complexes with NO.
Main Results:
- Both FeIII(DTPA)2- and FeIII(HDFB)+ demonstrated protective effects against septic shock.
- The iron-free ligand H4DFB+ showed significantly greater efficacy than DTPA.
- FeIII(DTPA)2- binds NO, while FeIII(HDFB)+ acts as an electrocatalyst for NO reduction to N2O.
Conclusions:
- Septic shock protection is mediated by NO scavenging and redox catalysis.
- Novel drugs targeting septic shock can be designed based on transition metal-mediated small molecule activation.
- Siderophore chemistry provides a foundation for developing new therapeutic agents.
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