期刊
JOURNAL OF CONTROLLED RELEASE
卷 349, 期 -, 页码 304-314出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.07.001
关键词
Methemoglobin; Hydrogensulfide; Antidote; Gasotransmitters; Poisoning; Cytochrome c oxidase
资金
- JST SPRING [JPMJSP2123]
In this study, methemoglobin-albumin clusters were developed as detoxifying agents for hydrogen sulfide (H2S) intoxication. These clusters have the ability to bind with H2S, thereby suppressing cell death and maintaining mitochondrial function. The results demonstrate that methemoglobin-albumin clusters possess suitable pharmacokinetic properties and biocompatibility for use as detoxifying agents against H2S intoxication.
Hydrogen sulfide (H2S) has attracted significant attention as a seed in drug development. However, H2S is toxic and induces lethal acute intoxication. Here, we developed methemoglobin (metHb)-albumin clusters as detox-ifying agents for H2S intoxication, which were designed based on the inherent binding property of metHb with H2S. The metHb-albumin clusters comprising an autoxidized ferric Hb center wrapped covalently with an average of three human serum albumins showed a similar H2S binding affinity to that of naked metHb. Owing to the H2S binding capability, metHb-albumin clusters suppressed cell death induced by H2S exposure while maintaining mitochondrial function in H9c2 cells. In addition, lethal H2S intoxication model mice were rescued by a single administration of metHb-albumin clusters, resulting from the recovery of cytochrome c oxidase ac-tivity. Furthermore, the metHb-albumin clusters possessed essential characteristics, such as adequate pharma-cokinetic properties and biocompatibility, for their use as detoxifying agents against H2S intoxication. In conclusion, the results obtained in this study suggest that metHb-albumin clusters are promising detoxifying agents for H2S intoxication and that harnessing the inherent H2S binding properties of metHb is an innovative approach to develop detoxifying agents for H2S intoxication.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据