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Hydrosulphide-methaemoglobin-albumin cluster: a hydrogen sulphide donor
Yuto Suzuki1, Taiga Yamada2, Yuki Enoki1
1Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Journal of Materials Chemistry. B
|October 17, 2024
Summary
Methaemoglobin (metHb) can be engineered into a hydrogen sulphide (H₂S) donor. This novel H₂S-metHb-albumin cluster effectively treats liver injury in mice, showing superior results and high safety.
Area of Science:
- Biomaterials Science
- Medicinal Chemistry
- Biochemistry
Background:
- Hydrogen sulphide (H₂S) exhibits significant antioxidant and anti-inflammatory properties.
- Methaemoglobin (metHb) can reversibly bind H₂S, suggesting its potential as an H₂S delivery system.
- Developing safe and effective H₂S donors is crucial for therapeutic applications.
Purpose of the Study:
- To engineer and characterize a novel H₂S donor using metHb and albumin.
- To evaluate the therapeutic efficacy of the H₂S-metHb-albumin cluster in a mouse model of hepatic ischemia-reperfusion injury.
- To compare the efficacy and safety of the novel H₂S donor with conventional H₂S donors.
Main Methods:
- Preparation and structural analysis of the H₂S-metHb-albumin cluster.
- Assessment of H₂S release kinetics and pH responsiveness.
- Evaluation of the cluster's protective effects in a murine model of hepatic ischemia-reperfusion injury.
- Toxicological and biological response assessment.
Main Results:
- The H₂S-metHb-albumin cluster demonstrated a nanostructure with sustained H₂S release, particularly at low pH.
- Treatment with the cluster significantly alleviated hepatic ischemia-reperfusion injury by reducing oxidative stress and inflammation.
- The H₂S-metHb-albumin cluster showed greater potency and higher biological compatibility than sodium hydrogen sulphide.
- No adverse toxic or biological effects were observed.
Conclusions:
- The H₂S-metHb-albumin cluster represents a promising and biocompatible H₂S donor for therapeutic applications.
- Methaemoglobin shows significant potential as a biomaterial for developing novel drug delivery systems.
- This study establishes the proof of concept for metHb-based H₂S delivery systems.
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