Food therapy of scutellarein ameliorates pirarubicin‑induced cardiotoxicity in rats by inhibiting apoptosis and ferroptosis through regulation of NOX2‑induced oxidative stress

Lan,Ying; Tian,Fengshun; Tang,Heng; Pu,Peng; He,Quan; Duan,Liang

doi:10.3892/mmr.2024.13208

Food therapy of scutellarein ameliorates pirarubicin‑induced cardiotoxicity in rats by inhibiting apoptosis and ferroptosis through regulation of NOX2‑induced oxidative stress

Authors:
- Ying Lan
- Fengshun Tian
- Heng Tang
- Peng Pu
- Quan He
- Liang Duan
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, P.R. China, Department of Endocrine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, P.R. China, Department of General Practice, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, P.R. China
Published online on: March 19, 2024 https://doi.org/10.3892/mmr.2024.13208
Article Number: 84
Copyright: © Lan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pirarubicin (THP) is one of the most commonly used antineoplastic drugs in clinical practice. However, its clinical application is limited due to its toxic and heart‑related side effects. It has been reported that oxidative stress, inflammation and apoptosis are closely associated with cardiotoxicity caused by pirarubicin (CTP). Additionally, it has also been reported that scutellarein (Sc) exerts anti‑inflammatory, antioxidant, cardio‑cerebral vascular protective and anti‑apoptotic properties. Therefore, the present study aimed to investigate the effect of food therapy with Sc on CTP and its underlying molecular mechanism using echocardiography, immunofluorescence, western blot, ROS staining, and TUNEL staining. The in vivo results demonstrated that THP was associated with cardiotoxicity. Additionally, abnormal changes in the expression of indicators associated with oxidative stress, ferroptosis and apoptosis were observed, which were restored by Sc. Therefore, it was hypothesized that CTP could be associated with oxidative stress, ferroptosis and apoptosis. Furthermore, the in vitro experiments showed that Sc and the NADPH oxidase 2 (NOX2) inhibitor, GSK2795039 (GSK), upregulated glutathione peroxidase 4 (GPX4) and inhibited THP‑induced oxidative stress, apoptosis and ferroptosis. However, cell treatment with the ferroptosis inhibitor, ferrostatin‑1, or inducer, erastin, could not significantly reduce or promote, respectively, the expression of NOX2. However, GSK significantly affected ferroptosis and GPX4 expression. Overall, the results of the present study indicated that food therapy with Sc ameliorated CTP via inhibition of apoptosis and ferroptosis through regulation of NOX2‑induced oxidative stress, thus suggesting that Sc may be a potential therapeutic drug against CTP.

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