Hydrosulphide-methaemoglobin-albumin cluster: a hydrogen sulphide donor.

Methaemoglobin (metHb) possesses inherent characteristics that facilitate reversible binding to hydrogen sulphide. Exogenous hydrogen sulphide supplementation imparts beneficial bioactive effects, including antioxidant and anti-inflammatory; hence, we hypothesized that the metHb-hydrogen sulphide complex could act as a hydrogen sulphide donor for medication. In this study, we prepared a hydrosulphide-metHb-albumin (H ₂ S-metHb-albumin) cluster and examined its applicability as a hydrogen sulphide donor in the mice model of hepatic ischemia-reperfusion injury. Structural analysis revealed that the H ₂ S-metHb-albumin cluster exhibited a nanostructure wherein one metHb was wrapped by an average of three albumins, and hydrogen sulphide was bound to the haem. Additionally, the H ₂ S-metHb-albumin cluster exhibited low-pH responsiveness, leading to sustained release of hydrogen sulphide. Owing to these structural and pharmaceutical characteristics, the severity of hepatic ischemia-reperfusion injury was alleviated via antioxidant and anti-inflammatory effects of the H ₂ S-metHb-albumin cluster treatment. The protective effects were more potent in the H ₂ S-metHb-albumin cluster compared to that in a conventional hydrogen sulphide donor (sodium hydrogen sulphide). No abnormal signs of toxic and biological responses were observed after the H ₂ S-metHb-albumin cluster administration, confirming high biological compatibility. These results successfully establish the proof of concept that the H ₂ S-metHb-albumin cluster is a promising hydrogen sulphide donor. To the best of our knowledge, this is the first report demonstrating the remarkable potential of metHb as a biomaterial for hydrogen sulphide donors.