Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 배옥남 | - |
dc.date.accessioned | 2020-01-28T04:36:07Z | - |
dc.date.available | 2020-01-28T04:36:07Z | - |
dc.date.issued | 2019-12 | - |
dc.identifier.citation | TOXICOLOGICAL SCIENCES, v. 172, No. 2, Page. 435-444 | en_US |
dc.identifier.issn | 1096-6080 | - |
dc.identifier.issn | 1096-0929 | - |
dc.identifier.uri | https://academic.oup.com/toxsci/article/172/2/435/5551365 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/122276 | - |
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. | en_US |
dc.description.sponsorship | This research was supported by a grant (#HI16C2044) of the Korea HealthTechnology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | OXFORD UNIV PRESS | en_US |
dc.subject | dapsone hydroxylamine (DDS-NHOH) | en_US |
dc.subject | thrombosis | en_US |
dc.subject | red blood cells (RBCs) | en_US |
dc.subject | phosphatidylserine (PS) exposure | en_US |
dc.subject | procoagulant activity | en_US |
dc.subject | reactive oxygen species (ROS) generation | en_US |
dc.title | Dapsone Hydroxylamine, an Active Metabolite of Dapsone, Can Promote the Procoagulant Activity of Red Blood Cells and Thrombosis | en_US |
dc.type | Article | en_US |
dc.relation.no | 2 | - |
dc.relation.volume | 172 | - |
dc.identifier.doi | 10.1093/toxsci/kfz188 | - |
dc.relation.page | 435-444 | - |
dc.relation.journal | TOXICOLOGICAL SCIENCES | - |
dc.contributor.googleauthor | Bian, Yiying | - |
dc.contributor.googleauthor | Kim, Keunyoung | - |
dc.contributor.googleauthor | An, Gwang-Jin | - |
dc.contributor.googleauthor | Ngo, Thien | - |
dc.contributor.googleauthor | Bae, Ok-Nam | - |
dc.contributor.googleauthor | Lim, Kyung-Min | - |
dc.contributor.googleauthor | Chung, Jin-Ho | - |
dc.relation.code | 2019000878 | - |
dc.sector.campus | E | - |
dc.sector.daehak | COLLEGE OF PHARMACY[E] | - |
dc.sector.department | DEPARTMENT OF PHARMACY | - |
dc.identifier.pid | onbae | - |
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