Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 임경민 | * |
dc.date.accessioned | 2020-01-14T16:30:16Z | - |
dc.date.available | 2020-01-14T16:30:16Z | - |
dc.date.issued | 2019 | * |
dc.identifier.issn | 1096-6080 | * |
dc.identifier.issn | 1096-0929 | * |
dc.identifier.other | OAK-26229 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/252408 | - |
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 | English | * |
dc.publisher | OXFORD UNIV PRESS | * |
dc.subject | dapsone hydroxylamine (DDS-NHOH) | * |
dc.subject | thrombosis | * |
dc.subject | red blood cells (RBCs) | * |
dc.subject | phosphatidylserine (PS) exposure | * |
dc.subject | procoagulant activity | * |
dc.subject | reactive oxygen species (ROS) generation | * |
dc.title | Dapsone Hydroxylamine, an Active Metabolite of Dapsone, Can Promote the Procoagulant Activity of Red Blood Cells and Thrombosis | * |
dc.type | Article | * |
dc.relation.issue | 2 | * |
dc.relation.volume | 172 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 435 | * |
dc.relation.lastpage | 444 | * |
dc.relation.journaltitle | TOXICOLOGICAL SCIENCES | * |
dc.identifier.doi | 10.1093/toxsci/kfz188 | * |
dc.identifier.wosid | WOS:000501738100017 | * |
dc.author.google | Bian, Yiying | * |
dc.author.google | Kim, Keunyoung | * |
dc.author.google | An, Gwang-Jin | * |
dc.author.google | Ngo, Thien | * |
dc.author.google | Bae, Ok-Nam | * |
dc.author.google | Lim, Kyung-Min | * |
dc.author.google | Chung, Jin-Ho | * |
dc.contributor.scopusid | 임경민(8916551700) | * |
dc.date.modifydate | 20240220115649 | * |