Melatonin alleviates doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, pyroptosis and apoptosis by activating Sirt1/Nrf2 pathway
Melatonin confers cardioprotective effects on multiple cardiovascular diseases, including doxorubicin-induced cardiomyopathy. The effectiveness of melatonin in mitigating myocardial injuries caused by Doxorubicin through enhancement of mitochondrial function is already established, however, the role...
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Elsevier
2023-06-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223003797 |
| _version_ | 1797837202703515648 |
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| author | Wei Zhang Xi Wang Yanhong Tang Congxin Huang |
| author_facet | Wei Zhang Xi Wang Yanhong Tang Congxin Huang |
| author_sort | Wei Zhang |
| collection | DOAJ |
| description | Melatonin confers cardioprotective effects on multiple cardiovascular diseases, including doxorubicin-induced cardiomyopathy. The effectiveness of melatonin in mitigating myocardial injuries caused by Doxorubicin through enhancement of mitochondrial function is already established, however, the role of melatonin in regulating the Sirtuin-1 (Sirt1)/Nuclear factor E2-associated factor 2 (Nrf2) pathway in lessening the onset of Doxorubicin-induced cardiomyopathy is yet to be elucidated. To address this, H9C2 cardiomyocytes and C57BL/6 mice were employed to construct in vitro and in vivo models of Dox-induced myocardial impairments, respectively. Results showed that Dox markedly evoked oxidative stress, pyroptosis and apoptosis both in vitro and in vivo, which were significantly alleviated by melatonin administration. Mechanistically, melatonin attenuated Dox-induced downregulation of Sirt1 and Nrf2, and both inhibition of Sirt1 and Nrf2 significantly reversed the cardioprotective effects of melatonin. In conclusion, our studies suggest that the activation of the Sirt1/Nrf2 pathway is the underlying mechanism behind melatonin's ability to curtail oxidative stress, pyroptosis, and apoptosis in Dox-induced cardiomyopathy. These promising results demonstrated the potential application of melatonin as a treatment for doxorubicin-induced cardiac injury. |
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| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T15:21:30Z |
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| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-f37b1ab7893148e09f0f1935dd473af52023-04-29T14:45:56ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-06-01162114591Melatonin alleviates doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, pyroptosis and apoptosis by activating Sirt1/Nrf2 pathwayWei Zhang0Xi Wang1Yanhong Tang2Congxin Huang3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China; Correspondence to: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Rd, Wuchang, Wuhan, 430060 Hubei, PR China.Melatonin confers cardioprotective effects on multiple cardiovascular diseases, including doxorubicin-induced cardiomyopathy. The effectiveness of melatonin in mitigating myocardial injuries caused by Doxorubicin through enhancement of mitochondrial function is already established, however, the role of melatonin in regulating the Sirtuin-1 (Sirt1)/Nuclear factor E2-associated factor 2 (Nrf2) pathway in lessening the onset of Doxorubicin-induced cardiomyopathy is yet to be elucidated. To address this, H9C2 cardiomyocytes and C57BL/6 mice were employed to construct in vitro and in vivo models of Dox-induced myocardial impairments, respectively. Results showed that Dox markedly evoked oxidative stress, pyroptosis and apoptosis both in vitro and in vivo, which were significantly alleviated by melatonin administration. Mechanistically, melatonin attenuated Dox-induced downregulation of Sirt1 and Nrf2, and both inhibition of Sirt1 and Nrf2 significantly reversed the cardioprotective effects of melatonin. In conclusion, our studies suggest that the activation of the Sirt1/Nrf2 pathway is the underlying mechanism behind melatonin's ability to curtail oxidative stress, pyroptosis, and apoptosis in Dox-induced cardiomyopathy. These promising results demonstrated the potential application of melatonin as a treatment for doxorubicin-induced cardiac injury.http://www.sciencedirect.com/science/article/pii/S0753332223003797MelatoninDoxorubicinCardiotoxicitySirt1Nrf2 |
| spellingShingle | Wei Zhang Xi Wang Yanhong Tang Congxin Huang Melatonin alleviates doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, pyroptosis and apoptosis by activating Sirt1/Nrf2 pathway Biomedicine & Pharmacotherapy Melatonin Doxorubicin Cardiotoxicity Sirt1 Nrf2 |
| title | Melatonin alleviates doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, pyroptosis and apoptosis by activating Sirt1/Nrf2 pathway |
| title_full | Melatonin alleviates doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, pyroptosis and apoptosis by activating Sirt1/Nrf2 pathway |
| title_fullStr | Melatonin alleviates doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, pyroptosis and apoptosis by activating Sirt1/Nrf2 pathway |
| title_full_unstemmed | Melatonin alleviates doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, pyroptosis and apoptosis by activating Sirt1/Nrf2 pathway |
| title_short | Melatonin alleviates doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, pyroptosis and apoptosis by activating Sirt1/Nrf2 pathway |
| title_sort | melatonin alleviates doxorubicin induced cardiotoxicity via inhibiting oxidative stress pyroptosis and apoptosis by activating sirt1 nrf2 pathway |
| topic | Melatonin Doxorubicin Cardiotoxicity Sirt1 Nrf2 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223003797 |
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