Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis
Abstract Doxorubicin (DOX) is an effective anti-tumor drug accompanied with many side effects, especially heart injury. To explore what effects of sophocarpine (SOP) on DOX-induced heart injury, this study conducted in vivo experiment and in vitro experiment, and the C57BL/6J mice and the H9C2 cells...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-51083-3 |
| _version_ | 1797363375066316800 |
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| author | Hong-jin Zhang Yang Fu Huang Zhang Ze-qun Lai Yi-Fei Dong |
| author_facet | Hong-jin Zhang Yang Fu Huang Zhang Ze-qun Lai Yi-Fei Dong |
| author_sort | Hong-jin Zhang |
| collection | DOAJ |
| description | Abstract Doxorubicin (DOX) is an effective anti-tumor drug accompanied with many side effects, especially heart injury. To explore what effects of sophocarpine (SOP) on DOX-induced heart injury, this study conducted in vivo experiment and in vitro experiment, and the C57BL/6J mice and the H9C2 cells were used. The experimental methods used included echocardiography, enzyme-linked immunosorbent assay (ELISA), dihydroethidium (DHE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, western blotting and so on. Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements of left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), while SOP reduced these indices. The relevant stainings showed that SOP reversed the increases of total superoxide level induced by DOX. DOX also contribute to a higher level of MDA and lower levels of SOD and GSH, but these changes were suppressed by SOP. DOX increased the pro-oxidative protein level of NOX-4 while decreased the anti-oxidative protein level of SOD-2, but SOP reversed these effects. In addition, this study further discovered that SOP inhibited the decreases of Nrf2 and HO-1 levels induced by DOX. The TUNEL staining revealed that SOP reduced the high degree of apoptosis induced by DOX. Besides, pro-apoptosis proteins like Bax, cleaved-caspase-3 and cytochrome-c upregulated while anti-apoptosis protein like Bcl-2 downregulated when challenged by DOX, but them were suppressed by SOP. These findings suggested that SOP could alleviate DOX-induced heart injury by suppressing oxidative stress and apoptosis, with molecular mechanism activating of the Nrf2/HO-1 signaling pathway. |
| first_indexed | 2024-03-08T16:20:29Z |
| format | Article |
| id | doaj.art-7718a32a1e984ceab8a222e1ecbb01c3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T16:20:29Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7718a32a1e984ceab8a222e1ecbb01c32024-01-07T12:22:51ZengNature PortfolioScientific Reports2045-23222024-01-0114111010.1038/s41598-023-51083-3Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosisHong-jin Zhang0Yang Fu1Huang Zhang2Ze-qun Lai3Yi-Fei Dong4Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang UniversityDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang UniversityDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang UniversityDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang UniversityDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang UniversityAbstract Doxorubicin (DOX) is an effective anti-tumor drug accompanied with many side effects, especially heart injury. To explore what effects of sophocarpine (SOP) on DOX-induced heart injury, this study conducted in vivo experiment and in vitro experiment, and the C57BL/6J mice and the H9C2 cells were used. The experimental methods used included echocardiography, enzyme-linked immunosorbent assay (ELISA), dihydroethidium (DHE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, western blotting and so on. Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements of left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), while SOP reduced these indices. The relevant stainings showed that SOP reversed the increases of total superoxide level induced by DOX. DOX also contribute to a higher level of MDA and lower levels of SOD and GSH, but these changes were suppressed by SOP. DOX increased the pro-oxidative protein level of NOX-4 while decreased the anti-oxidative protein level of SOD-2, but SOP reversed these effects. In addition, this study further discovered that SOP inhibited the decreases of Nrf2 and HO-1 levels induced by DOX. The TUNEL staining revealed that SOP reduced the high degree of apoptosis induced by DOX. Besides, pro-apoptosis proteins like Bax, cleaved-caspase-3 and cytochrome-c upregulated while anti-apoptosis protein like Bcl-2 downregulated when challenged by DOX, but them were suppressed by SOP. These findings suggested that SOP could alleviate DOX-induced heart injury by suppressing oxidative stress and apoptosis, with molecular mechanism activating of the Nrf2/HO-1 signaling pathway.https://doi.org/10.1038/s41598-023-51083-3 |
| spellingShingle | Hong-jin Zhang Yang Fu Huang Zhang Ze-qun Lai Yi-Fei Dong Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis Scientific Reports |
| title | Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis |
| title_full | Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis |
| title_fullStr | Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis |
| title_full_unstemmed | Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis |
| title_short | Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis |
| title_sort | sophocarpine alleviates doxorubicin induced heart injury by suppressing oxidative stress and apoptosis |
| url | https://doi.org/10.1038/s41598-023-51083-3 |
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