Work

Arsenic trioxide-induced cardiotoxicity: insights into the oxidative stress-inflammation positive feedback loop, translational biomarkers and targeted cardioprotective strategies— a narrative review

Year: 2026

Type: review

Abstract: Arsenic trioxide (ATO) is a first-line chemotherapeutic agent that achieves a complete remission rate above 90% in newly diagnosed acute promyelocytic leukemia, with indications expanding to multiple hematological malignancies and solid tumors. However, dose-dependent cardiotoxicity-manifesting as acute QTc prolongation and malignant arrhythmia, as well as chronic myocardial hypertrophy, interstitial fibrosis and progressive heart failure-remains a critical clinical barrier that limits its therapeutic window, and no approved targeted cardioprotective regimens are currently available in clinical practice. This narrative Mini Review proposes an integrated mechanistic framework centered on the oxidative stress-inflammation positive feedback loop, which complements the conventional view of two independent pathogenic pathways. In this framework, ATO-induced mitochondrial dysfunction and impaired Nrf2 antioxidant defense initiate oxidative stress as the upstream trigger; ROS subsequently drives inflammatory activation via NF-κB and NLRP3 inflammasome pathways, while sustained inflammation in turn aggravates oxidative damage by suppressing Nrf2 activity and disrupting mitochondrial homeostasis. This proposed self-amplifying loop exhibits spatiotemporal heterogeneity. It appears incompletely established in acute electrophysiological injury, but may serve as a potential mechanistic contributor to chronic structural remodeling. Based on this framework, this work summarizes dual-target cardioprotective strategies that preserve ATO's anti-tumor efficacy, and evaluates translational biomarkers for early risk stratification. Collectively, this review provides a mechanistic foundation for precision cardioprotection and clinical safety optimization of ATO-based chemotherapy.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1954263

Authors: Haiyan Wu, Jian Lv, Xiaoyang Hu

Institution: Heilongjiang University of Chinese Medicine

Language: English

Topic: Chemotherapy-induced cardiotoxicity and mitigation

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801