Sarmentosin alleviates doxorubicin-induced cardiotoxicity and ferroptosis via the p62-Keap1-Nrf2 pathway
Doxorubicin (Dox) is extensively used as an antitumor agent, but its severe cardiotoxicity significantly limits its clinical use. Current treatments for Dox-induced cardiotoxicity are inadequate, necessitating alternative solutions. This study evaluated the effects of sarmentosin, a compound from Se...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Redox Report |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/13510002.2024.2392329 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846138652531359744 |
|---|---|
| author | Zhihui Lin Chang Wu Dongyan Song Chenxi Zhu Bosen Wu Jie Wang Yangjing Xue |
| author_facet | Zhihui Lin Chang Wu Dongyan Song Chenxi Zhu Bosen Wu Jie Wang Yangjing Xue |
| author_sort | Zhihui Lin |
| collection | DOAJ |
| description | Doxorubicin (Dox) is extensively used as an antitumor agent, but its severe cardiotoxicity significantly limits its clinical use. Current treatments for Dox-induced cardiotoxicity are inadequate, necessitating alternative solutions. This study evaluated the effects of sarmentosin, a compound from Sedum sarmentosum, on Dox-induced cardiotoxicity and dysfunction. Sarmentosin was administered as a pretreatment to both mice and H9c2 cells before Dox exposure. Subsequently, markers of Dox-induced cardiotoxicity and ferroptosis in serum and cell supernatants were measured. Western blot analysis was utilized to detect levels of ferroptosis, oxidative stress, and autophagy proteins. Additionally, echocardiography, hematoxylin–eosin staining, ROS detection, and immunofluorescence techniques were employed to support our findings. Results demonstrated that sarmentosin significantly inhibited iron accumulation, lipid peroxidation, and oxidative stress, thereby reducing Dox-induced ferroptosis and cardiotoxicity in C57BL/6 mice and H9c2 cells. The mechanism involved the activation of autophagy and the Nrf2 signaling pathway. These findings suggest that sarmentosin may prevent Dox-induced cardiotoxicity by mitigating ferroptosis. The study underscores the potential of compounds like sarmentosin in treating Dox-induced cardiotoxicity. |
| format | Article |
| id | doaj-art-14cc80c6fc0b4843b95d6fcb312e7235 |
| institution | Kabale University |
| issn | 1351-0002 1743-2928 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Redox Report |
| spelling | doaj-art-14cc80c6fc0b4843b95d6fcb312e72352024-12-07T06:20:30ZengTaylor & Francis GroupRedox Report1351-00021743-29282024-12-0129110.1080/13510002.2024.2392329Sarmentosin alleviates doxorubicin-induced cardiotoxicity and ferroptosis via the p62-Keap1-Nrf2 pathwayZhihui Lin0Chang Wu1Dongyan Song2Chenxi Zhu3Bosen Wu4Jie Wang5Yangjing Xue6Department of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaDepartment of Endocrinology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaDepartment of Cardiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaDoxorubicin (Dox) is extensively used as an antitumor agent, but its severe cardiotoxicity significantly limits its clinical use. Current treatments for Dox-induced cardiotoxicity are inadequate, necessitating alternative solutions. This study evaluated the effects of sarmentosin, a compound from Sedum sarmentosum, on Dox-induced cardiotoxicity and dysfunction. Sarmentosin was administered as a pretreatment to both mice and H9c2 cells before Dox exposure. Subsequently, markers of Dox-induced cardiotoxicity and ferroptosis in serum and cell supernatants were measured. Western blot analysis was utilized to detect levels of ferroptosis, oxidative stress, and autophagy proteins. Additionally, echocardiography, hematoxylin–eosin staining, ROS detection, and immunofluorescence techniques were employed to support our findings. Results demonstrated that sarmentosin significantly inhibited iron accumulation, lipid peroxidation, and oxidative stress, thereby reducing Dox-induced ferroptosis and cardiotoxicity in C57BL/6 mice and H9c2 cells. The mechanism involved the activation of autophagy and the Nrf2 signaling pathway. These findings suggest that sarmentosin may prevent Dox-induced cardiotoxicity by mitigating ferroptosis. The study underscores the potential of compounds like sarmentosin in treating Dox-induced cardiotoxicity.https://www.tandfonline.com/doi/10.1080/13510002.2024.2392329SarmentosinDoxorubicincardiotoxicityautophagyferroptosis |
| spellingShingle | Zhihui Lin Chang Wu Dongyan Song Chenxi Zhu Bosen Wu Jie Wang Yangjing Xue Sarmentosin alleviates doxorubicin-induced cardiotoxicity and ferroptosis via the p62-Keap1-Nrf2 pathway Redox Report Sarmentosin Doxorubicin cardiotoxicity autophagy ferroptosis |
| title | Sarmentosin alleviates doxorubicin-induced cardiotoxicity and ferroptosis via the p62-Keap1-Nrf2 pathway |
| title_full | Sarmentosin alleviates doxorubicin-induced cardiotoxicity and ferroptosis via the p62-Keap1-Nrf2 pathway |
| title_fullStr | Sarmentosin alleviates doxorubicin-induced cardiotoxicity and ferroptosis via the p62-Keap1-Nrf2 pathway |
| title_full_unstemmed | Sarmentosin alleviates doxorubicin-induced cardiotoxicity and ferroptosis via the p62-Keap1-Nrf2 pathway |
| title_short | Sarmentosin alleviates doxorubicin-induced cardiotoxicity and ferroptosis via the p62-Keap1-Nrf2 pathway |
| title_sort | sarmentosin alleviates doxorubicin induced cardiotoxicity and ferroptosis via the p62 keap1 nrf2 pathway |
| topic | Sarmentosin Doxorubicin cardiotoxicity autophagy ferroptosis |
| url | https://www.tandfonline.com/doi/10.1080/13510002.2024.2392329 |
| work_keys_str_mv | AT zhihuilin sarmentosinalleviatesdoxorubicininducedcardiotoxicityandferroptosisviathep62keap1nrf2pathway AT changwu sarmentosinalleviatesdoxorubicininducedcardiotoxicityandferroptosisviathep62keap1nrf2pathway AT dongyansong sarmentosinalleviatesdoxorubicininducedcardiotoxicityandferroptosisviathep62keap1nrf2pathway AT chenxizhu sarmentosinalleviatesdoxorubicininducedcardiotoxicityandferroptosisviathep62keap1nrf2pathway AT bosenwu sarmentosinalleviatesdoxorubicininducedcardiotoxicityandferroptosisviathep62keap1nrf2pathway AT jiewang sarmentosinalleviatesdoxorubicininducedcardiotoxicityandferroptosisviathep62keap1nrf2pathway AT yangjingxue sarmentosinalleviatesdoxorubicininducedcardiotoxicityandferroptosisviathep62keap1nrf2pathway |