Protective effect of dioscin against doxorubicin-induced cardiotoxicity via adjusting microRNA-140-5p-mediated myocardial oxidative stress
Open accessAbstract
Clinical application of doxorubicin (DOX) is limited because of its cardiotoxicity. Thus, exploration of effective lead compounds against DOX-induced cardiotoxicity is necessary. The aim of the present study was to investigate the effects and possible mechanisms of dioscin against DOX-induced cardiotoxicity. The in vitro model of DOX- treated H9C2 cells and the in vivo models of DOX-treated rats and mice were used in this study. The results showed that discoin markedly increased H9C2 cell viability, decreased the levels of CK, LDH, and improved histopathological and electrocardio- gram changes in rats and mice to protect DOX-induced cardiotoxicity. Furthermore, dioscin significantly inhibited myocardial oxidative insult through adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px in vitro and in vivo. Our data also indicated that dioscin activated Nrf2 and Sirt2 signaling pathways, and thereby affected the expression levels of HO-1, NQO1, Gst, GCLM, Keap1 and FOXO3a through decreasing miR-140-5p expression level. In addition, the level of intracellular ROS was significantly increased in H9C2 cells treated by DOX after miR-140-5p mimic transfection, as well as the down-regulated expression levels of Nrf2 and Sirt2, which were markedly reversed by dioscin. In conclusion, our data suggested that dioscin alleviated DOX-induced cardiotoxicity through modulating miR-140-5p-mediated myocardial oxidative stress. This natural product should be developed as a new candidate to alleviate cardiotoxicity caused by DOX in the future.
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DOX is a cytotoxic drug which suffers from severe side effects such as cardiotoxicity.
“Previous studies have confirmed that DOX is a cytotoxic drug which suffered from severe side effects such as cardiotoxicity.58–60”
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- Authors
- Zhao, L., Tao, X., Qi, Y., Xu, L., Yin, L., & Peng, J.
- Affiliations
- Dalian Medical University (CN)
- Corresponding author
- Peng, Jinyong
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 16
- Pages
- 189-198
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC5953242
- OpenAlex
- W2789593555
- Cited by
- 202
- References
- 50
- Citations by year
- 2026: 3 · 2025: 14 · 2024: 32 · 2023: 29 · 2022: 37 · 2021: 33 · 2020: 26 · 2019: 15 · 2018: 13
- FWCI
- 16.43
- Type
- journal article
- Language
- en
- Update notices
- erratum (2019-09-01)
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Dalian Medical University (2015004)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
- Physical Sciences › Materials Science › Biomaterials › Phytochemistry and Bioactive Compounds
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- dioscin, doxorubicin cardiotoxicity, miR-140-5p, myocardial oxidative stress, Nrf2 signaling, H9c2 cells, reactive oxygen species, antioxidant enzymes, heme oxygenase-1, NQO1, Keap1, FOXO3, cardioprotection, anthracycline cardiotoxicity
- MeSH terms
- Animals, Cell Survival, Diosgenin, Doxorubicin, Myocardium, Neoplasm Proteins, Neoplasms, Gene Expression Regulation, Neoplastic, Apoptosis, Oxidative Stress, MicroRNAs, Mice, Rats, Cardiotoxicity
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