ArticleDrug design, development and therapy2021
Roflumilast Attenuates Doxorubicin-Induced Cardiotoxicity by Targeting Inflammation and Cellular Senescence in Cardiomyocytes Mediated by SIRT1.
Article in Drug design, development and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Mechanisms of Doxorubicin-Induced Cardiac Senescence and Potential Therapeutic Strategies.Biomolecules · 2026Review
- Chemokine-Guided Biomimetic Mn/Ce Nanozymes for Immunomodulation and Cardioprotection in Doxorubicin-Induced Cardiomyopathy.Advanced healthcare materials · 2026Article
- Ginkgetin Alleviates Doxorubicin-Induced Heart Failure by Regulating Mitochondrial Dysfunction Through the AMPK/Sirt1/NF-κB Signaling Pathway.Balkan medical journal · 2026Article
- Doxorubicin-Induced Cardiac Remodeling: Mechanisms and Mitigation Strategies.Cardiovascular drugs and therapy · 2026Review
- Sanggenol L Alleviates Rotenone-induced Parkinson's Disease, Inhibits Mitochondrial Complex ICombinatorial chemistry & high throughput screening · 2026Article
- Taxifolin Protects Against 5-Fluorouracil-Induced Cardiotoxicity in Mice Through Mitigating Oxidative Stress, Inflammation, and Apoptosis: Possible Involvement of Sirt1/Nrf2/HO-1 Signaling.Cardiovascular toxicology · 2025Article
- Efficacy and Safety of Roflumilast versus Alpha-Lipoic Acid in Type 2 Diabetes with Neuropathy: A Comparative Clinical Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- PI3K/AKT signaling activation by roflumilast ameliorates rotenone-induced Parkinson's disease in rats.Inflammopharmacology · 2024Article
- 4-Deoxy-Drug design, development and therapy · 2024Article
- Recent Advances in the Mechanisms of Cell Death and Dysfunction in Doxorubicin Cardiotoxicity.Reviews in cardiovascular medicine · 2023Review
- Inflammation and aging: signaling pathways and intervention therapies.Signal transduction and targeted therapy · 2023Review
- Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway.Experimental and therapeutic medicine · 2023Article
- Therapeutic opportunities for senolysis in cardiovascular disease.The FEBS journal · 2023Review
- Vitamin C modulates adrenaline-augmented gastric injury via cardiac troponin/creatine kinase pathway in Wistar rats.Iranian journal of basic medical sciences · 2023Article
- Activation of the sirtuin silent information regulator 1 pathway inhibits pathological myocardial remodeling.Frontiers in pharmacology · 2023Review
- Cellular Senescence in Cardiovascular Diseases: A Systematic Review.Aging and disease · 2022Review
- Cariporide Attenuates Doxorubicin-Induced Cardiotoxicity in Rats by Inhibiting Oxidative Stress, Inflammation and Apoptosis Partly Through Regulation of Akt/GSK-3β and Sirt1 Signaling Pathway.Frontiers in pharmacology · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeCardiotoxicity is an important side effect of the treatment of a malignant tumor with Doxorubicin. Currently, decreasing the dosage of Doxorubicin to alleviate the side effects on cardiac function is the common method to deal with the cardiotoxicity induced by Doxorubicin. The present study aims to investigate the therapeutic effects of Roflumilast on Doxorubicin-induced inflammation and cellular senescence, as well as the potential mechanism in H9c2 myocardial cells.
methodsThe injured cardiac cell model was established by incubation with 5 μmol/L Doxorubicin. MTT was used to evaluate the cell viability of treated H9c2 cardiac cells. The expression of 4-HNE was determined using an immunofluorescence assay. The gene expression levels of IL-17, IL-6, TNF-α, IL-4, PAI-1, p21, and SIRT1 were evaluated using qRT-PCR and the protein levels of Gpx4, PAI-1, p21, and SIRT1 were determined using Western blot analysis. Secretions of IL-17, IL-6, TNF-α, IL-4, CK-MB, and cTnI were measured using ELISA. Cellular senescence was assessed using SA-β-Gal staining. Si-RNA technology was used to knockdown the expression of SIRT1 in H9c2 cardiac cells.
resultsCell viability of H9c2 cardiac cells was significantly inhibited by Doxorubicin but rescued by Roflumilast. The upregulated 4-HNE and downregulated Gpx4 were reversed by Roflumilast. The secretions of IL-6 and IL-17 were promoted by Doxorubicin and suppressed by Roflumilast. The increased SA-β-Gal staining induced by Doxorubicin was inhibited by Roflumilast. P21 and PAI-1 were significantly upregulated and SIRT1 was greatly downregulated by Doxorubicin, all of which were reversed by Roflumilast. The anti-senescent effect of Roflumilast was abolished by knocking down SIRT1.
conclusionRoflumilast might attenuate Doxorubicin-induced inflammation and cellular senescence in cardiomyocytes by upregulating SIRT1.
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