Dipyridamole Acts as Clinical Ferroptosis Inhibitor to Prevent from Tissue Injury
Abstract Ferroptosis is a newly identified cell death triggered by iron‐induced lipid peroxidation. Numerous studies reveal that ferroptosis participates in multiple types of tissue injury including ischaemia–reperfusion (I/R) injury and doxorubicin (Dox)‐induced damage. Targeting ferroptosis is a p...
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Wiley
2025-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202500566 |
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| author | Xiao Zhuang Shuang Shi Shuo Liu Yaqiong Jiao Bin Huang Yinghong Yang Li Yang Xinquan Yang Hui Wang Chunhui Liang Dandan Song Huaxiang Yu Dan Zou Qi Sun Shu Yang Chengqian Yin Jian Li Yiming Liu Junxia Min Fudi Wang Yong Nian Lutao Du Bo Chu |
| author_facet | Xiao Zhuang Shuang Shi Shuo Liu Yaqiong Jiao Bin Huang Yinghong Yang Li Yang Xinquan Yang Hui Wang Chunhui Liang Dandan Song Huaxiang Yu Dan Zou Qi Sun Shu Yang Chengqian Yin Jian Li Yiming Liu Junxia Min Fudi Wang Yong Nian Lutao Du Bo Chu |
| author_sort | Xiao Zhuang |
| collection | DOAJ |
| description | Abstract Ferroptosis is a newly identified cell death triggered by iron‐induced lipid peroxidation. Numerous studies reveal that ferroptosis participates in multiple types of tissue injury including ischaemia–reperfusion (I/R) injury and doxorubicin (Dox)‐induced damage. Targeting ferroptosis is a promising approach for disease treatment as the blockade of ferroptosis efficiently alleviates the symptoms. However, no known ferroptosis inhibitors have been used for clinical treatment. Although certain clinical compounds act as ferroptosis inhibitors in vitro, whether these drugs cure tissue injury by suppressing ferroptosis is little known. Here, by screening a large panel of drugs used in the clinic, it is identified that dipyridamole significantly attenuates Dox or I/R‐induced cardiac injury. Moreover, dipyridamole can achieve a good therapeutic effect on liver and kidney injury. Mechanistically, dipyridamole‐mediated ferroptosis inhibition is strictly dependent on solute carrier family 7 member 11 (SLC7A11). Dipyridamole down‐regulates the expression of ring finger protein 126 (RNF126), which is an E3 ligase to ubiquitinate SLC7A11 for proteasome degradation. Deficiency of SLC7A11 largely blocks the protective role of dipyridamole in vitro and in vivo. Together, the findings uncover that dipyridamole acts as a clinical compound to alleviate organ injury via suppressing ferroptosis, providing novel insights into the clinical therapy for ferroptosis‐related tissue damage. |
| format | Article |
| id | doaj-art-737520d3a1504ce58bae44d3eec73e38 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-737520d3a1504ce58bae44d3eec73e382025-08-20T02:36:40ZengWileyAdvanced Science2198-38442025-06-011223n/an/a10.1002/advs.202500566Dipyridamole Acts as Clinical Ferroptosis Inhibitor to Prevent from Tissue InjuryXiao Zhuang0Shuang Shi1Shuo Liu2Yaqiong Jiao3Bin Huang4Yinghong Yang5Li Yang6Xinquan Yang7Hui Wang8Chunhui Liang9Dandan Song10Huaxiang Yu11Dan Zou12Qi Sun13Shu Yang14Chengqian Yin15Jian Li16Yiming Liu17Junxia Min18Fudi Wang19Yong Nian20Lutao Du21Bo Chu22Department of Cell Biology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 ChinaDepartment of Clinical Laboratory The Second Hospital of Shandong University Jinan 250012 ChinaDepartment of Cell Biology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 ChinaDepartment of General Practice Qilu Hospital of Shandong University Jinan 250012 ChinaInstitute for Cancer Research Shenzhen Bay Laboratory Shenzhen 518107 ChinaDepartment of Cell Biology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 ChinaDepartment of Respiratory and Critical Care Medicine Zhengzhou University People's Hospital Henan Provincial People's Hospital Zhengzhou 450003 ChinaThe First Affiliated Hospital Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaInstitute for Cancer Research Shenzhen Bay Laboratory Shenzhen 518107 ChinaDepartment of Cell Biology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 ChinaDepartment of Cell Biology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 ChinaDepartment of Emergency Medicine and Chest Pain Center Qilu Hospital of Shandong University Jinan 250012 ChinaDepartment of Emergency Medicine and Chest Pain Center Qilu Hospital of Shandong University Jinan 250012 ChinaDepartment of Biochemistry and Molecular Biology Shandong University School of Medicine Jinan 250012 ChinaCollege of Pharmacy Nanjing drum tower hospital Nanjing University of Chinese Medicine Nanjing 210023 ChinaInstitute for Cancer Research Shenzhen Bay Laboratory Shenzhen 518107 ChinaDepartment of Biochemistry and Molecular Biology Shandong University School of Medicine Jinan 250012 ChinaDepartment of Neurology Qilu Hospital of Shandong University Jinan 250012 ChinaThe First Affiliated Hospital Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou 310058 ChinaThe First Affiliated Hospital The Second Affiliated Hospital Institute of Translational Medicine School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine Hangzhou 310058 ChinaCollege of Pharmacy Nanjing drum tower hospital Nanjing University of Chinese Medicine Nanjing 210023 ChinaDepartment of Clinical Laboratory Qilu Hospital of Shandong University Jinan 250012 ChinaDepartment of Cell Biology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 ChinaAbstract Ferroptosis is a newly identified cell death triggered by iron‐induced lipid peroxidation. Numerous studies reveal that ferroptosis participates in multiple types of tissue injury including ischaemia–reperfusion (I/R) injury and doxorubicin (Dox)‐induced damage. Targeting ferroptosis is a promising approach for disease treatment as the blockade of ferroptosis efficiently alleviates the symptoms. However, no known ferroptosis inhibitors have been used for clinical treatment. Although certain clinical compounds act as ferroptosis inhibitors in vitro, whether these drugs cure tissue injury by suppressing ferroptosis is little known. Here, by screening a large panel of drugs used in the clinic, it is identified that dipyridamole significantly attenuates Dox or I/R‐induced cardiac injury. Moreover, dipyridamole can achieve a good therapeutic effect on liver and kidney injury. Mechanistically, dipyridamole‐mediated ferroptosis inhibition is strictly dependent on solute carrier family 7 member 11 (SLC7A11). Dipyridamole down‐regulates the expression of ring finger protein 126 (RNF126), which is an E3 ligase to ubiquitinate SLC7A11 for proteasome degradation. Deficiency of SLC7A11 largely blocks the protective role of dipyridamole in vitro and in vivo. Together, the findings uncover that dipyridamole acts as a clinical compound to alleviate organ injury via suppressing ferroptosis, providing novel insights into the clinical therapy for ferroptosis‐related tissue damage.https://doi.org/10.1002/advs.202500566dipyridamoleferroptosisSLC7A11tissue injury |
| spellingShingle | Xiao Zhuang Shuang Shi Shuo Liu Yaqiong Jiao Bin Huang Yinghong Yang Li Yang Xinquan Yang Hui Wang Chunhui Liang Dandan Song Huaxiang Yu Dan Zou Qi Sun Shu Yang Chengqian Yin Jian Li Yiming Liu Junxia Min Fudi Wang Yong Nian Lutao Du Bo Chu Dipyridamole Acts as Clinical Ferroptosis Inhibitor to Prevent from Tissue Injury Advanced Science dipyridamole ferroptosis SLC7A11 tissue injury |
| title | Dipyridamole Acts as Clinical Ferroptosis Inhibitor to Prevent from Tissue Injury |
| title_full | Dipyridamole Acts as Clinical Ferroptosis Inhibitor to Prevent from Tissue Injury |
| title_fullStr | Dipyridamole Acts as Clinical Ferroptosis Inhibitor to Prevent from Tissue Injury |
| title_full_unstemmed | Dipyridamole Acts as Clinical Ferroptosis Inhibitor to Prevent from Tissue Injury |
| title_short | Dipyridamole Acts as Clinical Ferroptosis Inhibitor to Prevent from Tissue Injury |
| title_sort | dipyridamole acts as clinical ferroptosis inhibitor to prevent from tissue injury |
| topic | dipyridamole ferroptosis SLC7A11 tissue injury |
| url | https://doi.org/10.1002/advs.202500566 |
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