Biomimetic Nanozymes Suppressed Ferroptosis to Ameliorate Doxorubicin-Induced Cardiotoxicity via Synergetic Effect of Antioxidant Stress and GPX4 Restoration
Mitochondria-dependent ferroptosis plays an important role in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity (DIC), which remains a clinical challenge due to the lack of effective interventions. Cerium oxide (CeO<sub>2</sub>), a representative nanozyme, has attracted much a...
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MDPI AG
2023-02-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/5/1090 |
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| author | Yunpeng Zhang Shuang Liu Jing Peng Shifeng Cheng Qingling Zhang Nan Zhang Zandong Zhou Yue Zhang Yang Zhao Tong Liu |
| author_facet | Yunpeng Zhang Shuang Liu Jing Peng Shifeng Cheng Qingling Zhang Nan Zhang Zandong Zhou Yue Zhang Yang Zhao Tong Liu |
| author_sort | Yunpeng Zhang |
| collection | DOAJ |
| description | Mitochondria-dependent ferroptosis plays an important role in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity (DIC), which remains a clinical challenge due to the lack of effective interventions. Cerium oxide (CeO<sub>2</sub>), a representative nanozyme, has attracted much attention because of its antioxidant properties. This study evaluated CeO<sub>2</sub>-based nanozymes for the prevention and treatment of DIC in vitro and in vivo by adding nanoparticles (NPs), which were synthesized by biomineralization, to the culture or giving them to the mice, and the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) was used as control. The prepared NPs exhibited an excellent antioxidant response and glutathione peroxidase 4 (GPX4)-depended bioregulation, with the additional merits of bio-clearance and long retention in the heart. The experiments showed that NP treatment could significantly reverse myocardial structural and electrical remodeling, and reduce myocardial necrosis. These cardioprotective therapeutic effects were associated with their ability to alleviate oxidative stress, mitochondrial lipid peroxidation, and mitochondrial membrane potential damage, with a superior efficiency to the Fer-1. The study also found that the NPs significantly restored the expression of GPX4 and mitochondrial-associated proteins, thereby restoring mitochondria-dependent ferroptosis. Therefore, the study provides some insights into the role of ferroptosis in DIC. It also shows that CeO<sub>2</sub>-based nanozymes could be a promising prevention and treatment candidate as a novel cardiomyocyte ferroptosis protector to mitigate DIC and improve prognosis and quality of life in cancer patients. |
| first_indexed | 2024-03-11T07:15:29Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T07:15:29Z |
| publishDate | 2023-02-01 |
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| series | Nutrients |
| spelling | doaj.art-5dbc7ad142814b09bdaf312a8a31b7dc2023-11-17T08:19:26ZengMDPI AGNutrients2072-66432023-02-01155109010.3390/nu15051090Biomimetic Nanozymes Suppressed Ferroptosis to Ameliorate Doxorubicin-Induced Cardiotoxicity via Synergetic Effect of Antioxidant Stress and GPX4 RestorationYunpeng Zhang0Shuang Liu1Jing Peng2Shifeng Cheng3Qingling Zhang4Nan Zhang5Zandong Zhou6Yue Zhang7Yang Zhao8Tong Liu9Department of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaDepartment of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaDepartment of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaDepartment of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaDepartment of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaDepartment of Radiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaDepartment of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaMitochondria-dependent ferroptosis plays an important role in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity (DIC), which remains a clinical challenge due to the lack of effective interventions. Cerium oxide (CeO<sub>2</sub>), a representative nanozyme, has attracted much attention because of its antioxidant properties. This study evaluated CeO<sub>2</sub>-based nanozymes for the prevention and treatment of DIC in vitro and in vivo by adding nanoparticles (NPs), which were synthesized by biomineralization, to the culture or giving them to the mice, and the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) was used as control. The prepared NPs exhibited an excellent antioxidant response and glutathione peroxidase 4 (GPX4)-depended bioregulation, with the additional merits of bio-clearance and long retention in the heart. The experiments showed that NP treatment could significantly reverse myocardial structural and electrical remodeling, and reduce myocardial necrosis. These cardioprotective therapeutic effects were associated with their ability to alleviate oxidative stress, mitochondrial lipid peroxidation, and mitochondrial membrane potential damage, with a superior efficiency to the Fer-1. The study also found that the NPs significantly restored the expression of GPX4 and mitochondrial-associated proteins, thereby restoring mitochondria-dependent ferroptosis. Therefore, the study provides some insights into the role of ferroptosis in DIC. It also shows that CeO<sub>2</sub>-based nanozymes could be a promising prevention and treatment candidate as a novel cardiomyocyte ferroptosis protector to mitigate DIC and improve prognosis and quality of life in cancer patients.https://www.mdpi.com/2072-6643/15/5/1090doxorubicin-induced cardiomyopathyferroptosismitochondriananozymeoxidative stressbiomineralization |
| spellingShingle | Yunpeng Zhang Shuang Liu Jing Peng Shifeng Cheng Qingling Zhang Nan Zhang Zandong Zhou Yue Zhang Yang Zhao Tong Liu Biomimetic Nanozymes Suppressed Ferroptosis to Ameliorate Doxorubicin-Induced Cardiotoxicity via Synergetic Effect of Antioxidant Stress and GPX4 Restoration Nutrients doxorubicin-induced cardiomyopathy ferroptosis mitochondria nanozyme oxidative stress biomineralization |
| title | Biomimetic Nanozymes Suppressed Ferroptosis to Ameliorate Doxorubicin-Induced Cardiotoxicity via Synergetic Effect of Antioxidant Stress and GPX4 Restoration |
| title_full | Biomimetic Nanozymes Suppressed Ferroptosis to Ameliorate Doxorubicin-Induced Cardiotoxicity via Synergetic Effect of Antioxidant Stress and GPX4 Restoration |
| title_fullStr | Biomimetic Nanozymes Suppressed Ferroptosis to Ameliorate Doxorubicin-Induced Cardiotoxicity via Synergetic Effect of Antioxidant Stress and GPX4 Restoration |
| title_full_unstemmed | Biomimetic Nanozymes Suppressed Ferroptosis to Ameliorate Doxorubicin-Induced Cardiotoxicity via Synergetic Effect of Antioxidant Stress and GPX4 Restoration |
| title_short | Biomimetic Nanozymes Suppressed Ferroptosis to Ameliorate Doxorubicin-Induced Cardiotoxicity via Synergetic Effect of Antioxidant Stress and GPX4 Restoration |
| title_sort | biomimetic nanozymes suppressed ferroptosis to ameliorate doxorubicin induced cardiotoxicity via synergetic effect of antioxidant stress and gpx4 restoration |
| topic | doxorubicin-induced cardiomyopathy ferroptosis mitochondria nanozyme oxidative stress biomineralization |
| url | https://www.mdpi.com/2072-6643/15/5/1090 |
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