Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species Production
Dabigatran is a novel oral anticoagulant that directly inhibits free and fibrin-bound thrombins and exerts rapid and predictable anticoagulant effects. While the use of this reagent has been associated with an increased risk of gastrointestinal bleeding, the reason why dabigatran use increases gastr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2508 |
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| author | Hiromi Kurokawa Atsushi Taninaka Hidemi Shigekawa Hirofumi Matsui |
| author_facet | Hiromi Kurokawa Atsushi Taninaka Hidemi Shigekawa Hirofumi Matsui |
| author_sort | Hiromi Kurokawa |
| collection | DOAJ |
| description | Dabigatran is a novel oral anticoagulant that directly inhibits free and fibrin-bound thrombins and exerts rapid and predictable anticoagulant effects. While the use of this reagent has been associated with an increased risk of gastrointestinal bleeding, the reason why dabigatran use increases gastrointestinal bleeding risk remains unknown. We investigated the cytotoxicity of dabigatran etexilate and tartaric acid, the two primary components of dabigatran. The cytotoxicity of dabigatran etexilate and tartaric acid was measured in a cell viability assay. Intracellular mitochondrial reactive oxygen species (mitROS) production and lipid peroxidation were measured using fluorescence dyes. Cell membrane viscosity was measured using atomic force microscopy. The potential of ascorbic acid as an inhibitor of dabigatran cytotoxicity was also evaluated. The cytotoxicity of dabigatran etexilate was higher than that of tartaric acid. Dabigatran etexilate induced mitROS production and lipid peroxidation and altered the cell membrane viscosity. Ascorbic acid inhibited the cytotoxicity and mitROS production induced by dabigatran etexilate. Therefore, we attributed the cytotoxicity of dabigatran to dabigatran etexilate, and proposed that the cytotoxic effects of dabigatran etexilate are mediated via mitROS production. Additionally, we demonstrated that dabigatran cytotoxicity can be prevented via antioxidant treatment. |
| first_indexed | 2024-03-10T06:41:02Z |
| format | Article |
| id | doaj.art-f62faf49c70a49c4a3fd6f89835e71bf |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:41:02Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f62faf49c70a49c4a3fd6f89835e71bf2023-11-22T17:44:49ZengMDPI AGCells2073-44092021-09-011010250810.3390/cells10102508Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species ProductionHiromi Kurokawa0Atsushi Taninaka1Hidemi Shigekawa2Hirofumi Matsui3Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8571, JapanFaculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8573, JapanFaculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8573, JapanFaculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8571, JapanDabigatran is a novel oral anticoagulant that directly inhibits free and fibrin-bound thrombins and exerts rapid and predictable anticoagulant effects. While the use of this reagent has been associated with an increased risk of gastrointestinal bleeding, the reason why dabigatran use increases gastrointestinal bleeding risk remains unknown. We investigated the cytotoxicity of dabigatran etexilate and tartaric acid, the two primary components of dabigatran. The cytotoxicity of dabigatran etexilate and tartaric acid was measured in a cell viability assay. Intracellular mitochondrial reactive oxygen species (mitROS) production and lipid peroxidation were measured using fluorescence dyes. Cell membrane viscosity was measured using atomic force microscopy. The potential of ascorbic acid as an inhibitor of dabigatran cytotoxicity was also evaluated. The cytotoxicity of dabigatran etexilate was higher than that of tartaric acid. Dabigatran etexilate induced mitROS production and lipid peroxidation and altered the cell membrane viscosity. Ascorbic acid inhibited the cytotoxicity and mitROS production induced by dabigatran etexilate. Therefore, we attributed the cytotoxicity of dabigatran to dabigatran etexilate, and proposed that the cytotoxic effects of dabigatran etexilate are mediated via mitROS production. Additionally, we demonstrated that dabigatran cytotoxicity can be prevented via antioxidant treatment.https://www.mdpi.com/2073-4409/10/10/2508dabigatran etexilatemitochondrial reactive oxygen specieslipid peroxidationatomic force microscopyantioxidant |
| spellingShingle | Hiromi Kurokawa Atsushi Taninaka Hidemi Shigekawa Hirofumi Matsui Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species Production Cells dabigatran etexilate mitochondrial reactive oxygen species lipid peroxidation atomic force microscopy antioxidant |
| title | Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species Production |
| title_full | Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species Production |
| title_fullStr | Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species Production |
| title_full_unstemmed | Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species Production |
| title_short | Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species Production |
| title_sort | dabigatran etexilate induces cytotoxicity in rat gastric epithelial cell line via mitochondrial reactive oxygen species production |
| topic | dabigatran etexilate mitochondrial reactive oxygen species lipid peroxidation atomic force microscopy antioxidant |
| url | https://www.mdpi.com/2073-4409/10/10/2508 |
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