Work

Idebenone protects against doxorubicin-induced cardiac injury by inhibiting ferroptosis in cardiomyocytes

Year: 2026

Type: article

Abstract: Heart failure (HF) remains a global health challenge with limited efficacious therapies, necessitating novel strategies targeting its underlying pathological mechanisms. Emerging evidence implicates dysregulated iron metabolism and ferroptosis-an iron-dependent form of regulated cell death-as critical drivers of cardiomyocyte attrition in heart failure pathogenesis. This study investigates the therapeutic potential of idebenone (IDE), a clinically approved mitochondrial-targeted antioxidant and short-chain analog of coenzyme Q10, in modulating ferroptosis-mediated cardiac dysfunction. We confirmed that idebenone significantly attenuated pathological markers of cardiac stress, reducing expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cardiomyocytes. Furthermore, idebenone treatment suppressed lipid peroxidation and mitochondrial iron overload. In the HF animal model, idebenone administration improved left ventricular ejection fraction, restored redox homeostasis and reduced cardiac iron deposition. These findings establish idebenone as a promising strategy to mitigate ferroptosis-driven myocardial injury, providing a translational framework for developing idebenone-based therapies for heart failure management. • Idebenone inhibits ferroptosis in Ang II-stimulated cardiomyocytes by reducing lipid peroxidation, iron accumulation, ROS, and boosting GPX4/Nrf2 expression. • In Dox-induced HF mice, idebenone improves LVEF/LVFS, alleviates fibrosis, and balances MDA/GSH levels, matching ferrostatin-1 effects. • Findings suggest idebenone's repurposing for HF therapy via ferroptosis modulation, despite limitations in cell lines and single-sex models.

Source: Experimental Gerontology

DOI: 10.1016/j.exger.2026.113039

Authors: Jie Mao, Zhiyi Zhou, Yuting Xu, Hangbo Qu, Bo Ma, Yihua Yu

Institutions: Zhejiang Chinese Medical University, First People's Hospital of Yuhang District, Zhejiang Hospital

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,400