TY  - JOUR
T1  - Roflumilast Protects Cardiomyocytes from Doxorubicin-Induced Damage by Modulating Inflammatory Responses and Cellular Aging via SIRT1
A1  - Mohamed Abdelrahman
A1  - Saif Osman
JF  - Pharmaceutical Sciences and Drug Design
JO  - Pharm Sci Drug Des
SN  - 3062-4428
Y1  - 2025
VL  - 5
IS  - 1
DO  - 10.51847/Dh6x6Hnj1J
SP  - 205
EP  - 216
N2  - Doxorubicin is widely used for cancer therapy but is limited by its cardiotoxic effects. Traditional approaches, such as lowering the drug dose, aim to reduce cardiac side effects but may compromise anticancer efficacy. This study investigates whether Roflumilast can protect heart cells from Doxorubicin-induced inflammation and premature cellular aging, and explores the role of SIRT1 in this process. H9c2 cardiomyocytes were exposed to 5 μmol/L Doxorubicin to induce cell injury. Cell survival was measured using the MTT assay. Levels of oxidative stress marker 4-HNE were assessed by immunofluorescence. Gene expression of pro- and anti-inflammatory cytokines (IL-6, IL-17, TNF-α, IL-4) and senescence-related markers (p21, PAI-1, SIRT1) were evaluated using qRT-PCR, while Western blot measured protein levels of Gpx4, PAI-1, p21, and SIRT1. Secretion of cytokines and cardiac injury markers (CK-MB, cTnI) was quantified by ELISA. Cellular senescence was examined with SA-β-Gal staining. To determine the involvement of SIRT1, its expression was silenced using siRNA in H9c2 cells. Doxorubicin markedly reduced cardiomyocyte viability and induced oxidative stress, inflammatory cytokine release, and cellular senescence. Treatment with Roflumilast reversed these effects, restoring cell viability, reducing 4-HNE levels, suppressing IL-6 and IL-17 secretion, and decreasing SA-β-Gal staining. Roflumilast also counteracted Doxorubicin-induced increases in p21 and PAI-1 and restored SIRT1 expression. Silencing SIRT1 abolished the protective, anti-senescent effects of Roflumilast, confirming that SIRT1 mediates its cardioprotective action. Roflumilast demonstrates potential as a cardioprotective agent against Doxorubicin-induced damage by limiting inflammation and cellular aging, primarily through SIRT1 activation.
UR  - https://galaxypub.co/article/roflumilast-protects-cardiomyocytes-from-doxorubicin-induced-damage-by-modulating-inflammatory-respo-i9cvrnrunxll1qb
ER  -