Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
J Mater Chem B. 2024 Nov 13;12(44):11515-11522. doi: 10.1039/d4tb01621a.
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 (HS-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 HS-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 HS-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 antioxidant and anti-inflammatory effects of the HS-metHb-albumin cluster treatment. The protective effects were more potent in the HS-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 HS-metHb-albumin cluster administration, confirming high biological compatibility. These results successfully establish the proof of concept that the HS-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.
高铁血红蛋白（metHb）具有固有特性，可与硫化氢可逆结合。外源性硫化氢补充可产生有益的生物活性效应，包括抗氧化和抗炎作用；因此，我们假设 metHb-硫化氢复合物可以作为药物的硫化氢供体。在这项研究中，我们制备了一种巯基化 metHb-白蛋白（HS-metHb-albumin）簇，并在肝缺血再灌注损伤的小鼠模型中检验了其作为硫化氢供体的适用性。结构分析表明，HS-metHb-albumin 簇呈现纳米结构，其中一个 metHb 被平均三个白蛋白包裹，并且硫化氢与血红素结合。此外，HS-metHb-albumin 簇表现出对低 pH 的响应性，导致硫化氢的持续释放。由于这些结构和药物特性，肝缺血再灌注损伤的严重程度得到缓解，这归因于 HS-metHb-albumin 簇治疗的抗氧化和抗炎作用。与传统的硫化氢供体（硫氢化钠）相比，HS-metHb-albumin 簇的保护作用更强。HS-metHb-albumin 簇给药后未观察到毒性和生物学反应的异常迹象，证实了其具有较高的生物相容性。这些结果成功地证明了 HS-metHb-albumin 簇是一种有前途的硫化氢供体的概念验证。据我们所知，这是首次报道高铁血红蛋白作为硫化氢供体生物材料的显著潜力。
