Dapsone Hydroxylamine, an Active Metabolite of Dapsone, Can Promote the Procoagulant Activity of Red Blood Cells and Thrombosis
DC Field | Value | Language |
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dc.contributor.author | Bian, Yiying | - |
dc.contributor.author | Kim, Keunyoung | - |
dc.contributor.author | An, Gwang-Jin | - |
dc.contributor.author | Ngo, Thien | - |
dc.contributor.author | Bae, Ok-Nam | - |
dc.contributor.author | Lim, Kyung-Min | - |
dc.contributor.author | Chung, Jin-Ho | - |
dc.date.accessioned | 2021-06-22T09:25:07Z | - |
dc.date.available | 2021-06-22T09:25:07Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2019-12 | - |
dc.identifier.issn | 1096-6080 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/2006 | - |
dc.description.abstract | Dapsone hydroxylamine (DDS-NHOH), N-hydroxylated metabolite of a sulfonamide antibiotic, dapsone, is responsible for various adverse effects of dapsone that include methemoglobinemia, hemolytic anemia, and thrombosis. However, the mechanism underlying DDS-NHOH-induced thrombosis remains unclear. Here, we demonstrated that DDS-NHOH, but not dapsone, could increase prothrombotic risks through inducing the procoagulant activity of red blood cells (RBCs). In freshly isolated human RBCs in vitro, sub-hemolytic concentrations of DDS-NHOH (10-50 mu M) increased phosphatidylserine (PS) exposure and augmented the formation of PS-bearing microvesicles (MV). Reactive oxygen species (ROS) generation and the subsequent dysregulation of enzymes maintaining membrane phospholipid asymmetry were found to induce the procoagulant activity of DDS-NHOH. Dapsone hydroxylamine also accelerated thrombin generation and enhanced RBC self-aggregation and adherence of RBCs to endothelial cells in vitro. Most importantly, both the single dose of 50 or 100 mg/kg (i.p.) DDS-NHOH and repeated doses of 10 mg/kg per day (i.p.) for 4 days increased thrombus formation in rats (six rats per dose) in vivo, substantiating a potential prothrombotic risk of DDS-NHOH. Collectively, these results demonstrated the central role of RBC procoagulant activity induced by DDS-NHOH in the thrombotic risk of dapsone. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | OXFORD UNIV PRESS | - |
dc.title | Dapsone Hydroxylamine, an Active Metabolite of Dapsone, Can Promote the Procoagulant Activity of Red Blood Cells and Thrombosis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Bae, Ok-Nam | - |
dc.identifier.doi | 10.1093/toxsci/kfz188 | - |
dc.identifier.scopusid | 2-s2.0-85075813911 | - |
dc.identifier.wosid | 000501738100017 | - |
dc.identifier.bibliographicCitation | TOXICOLOGICAL SCIENCES, v.172, no.2, pp.435 - 444 | - |
dc.relation.isPartOf | TOXICOLOGICAL SCIENCES | - |
dc.citation.title | TOXICOLOGICAL SCIENCES | - |
dc.citation.volume | 172 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 435 | - |
dc.citation.endPage | 444 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Toxicology | - |
dc.relation.journalWebOfScienceCategory | Toxicology | - |
dc.subject.keywordPlus | HEMOLYTIC-ANEMIA | - |
dc.subject.keywordPlus | GENERATION | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | TRANSPLANTATION | - |
dc.subject.keywordPlus | ERYTHROCYTES | - |
dc.subject.keywordPlus | PROPHYLAXIS | - |
dc.subject.keywordPlus | FLIPPASES | - |
dc.subject.keywordPlus | TOXICITY | - |
dc.subject.keywordPlus | ROS | - |
dc.subject.keywordAuthor | dapsone hydroxylamine (DDS-NHOH) | - |
dc.subject.keywordAuthor | thrombosis | - |
dc.subject.keywordAuthor | red blood cells (RBCs) | - |
dc.subject.keywordAuthor | phosphatidylserine (PS) exposure | - |
dc.subject.keywordAuthor | procoagulant activity | - |
dc.subject.keywordAuthor | reactive oxygen species (ROS) generation | - |
dc.identifier.url | https://academic.oup.com/toxsci/article/172/2/435/5551365 | - |
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