Oxidative Stress and Pyroptosis in Doxorubicin-Induced Heart Failure and Atrial Fibrillation

Abstract

Patients undergoing doxorubicin (Dox) chemotherapy often develop new-onset atrial fibrillation and heart failure. Recent studies indicate that the TLR4/MyD88/NLRP3 pyroptosis signaling pathway plays a key role in the occurrence and development of cancer, heart failure, and atherosclerosis. However, few studies investigated the role of oxidative stress and pyroptosis in doxorubicin-induced heart failure and new-onset atrial fibrillation. In this study, we recruited 84 healthy subjects, 112 patients undergoing Dox chemotherapy showing heart failure (HF), and 62 patients undergoing Dox treatment who manifested atrial fibrillation (AF). The mRNA and protein levels of TLR4 expression, several downstream pyroptosis-associated proteins (cleaved caspase-1, NLRP3, GSDMD-N, and HMGB-1), serum inflammatory factors, and oxidative stress were detected at the beginning of chemotherapy and after 3 months of Dox chemotherapy. Oxidative stress and downstream pyroptosis-associated proteins tended to increase in the Dox-baseline group to the Dox-HF group. However, virtually no change in the expression of either oxidative stress or pyroptosis-associated proteins was detected in patients after three months of Dox chemotherapy compared with those at baseline. This study suggests that the prolonged oxidative stress and high levels of pyroptosis-associated proteins contribute to cardiac systolic dysfunction, suggesting TLR4 as a novel biomarker and a potential treatment target for doxorubicin-induced heart failure.

Anticancer Therapies Based on Oxidative Damage: Lycium barbarum Inhibits the Proliferation of MCF-7 Cells by Activating Pyroptosis through Endoplasmic Reticulum Stress

“…Considering the potential pro-oxidant action of natural extracts on cancer cells and given that oxidative stress is a significant inducer of pyroptosis [ 85 , 86 ], intracellular ROS production following LBE treatment was evaluated. To this end, MCF-7 cells were treated with LBE (6 μg/mL) from 1 to 24 h, followed by the determination of ROS levels using DCFH-DA as the fluorescent agent.…”

Creatine and Resistance Training: A Combined Approach to Attenuate Doxorubicin-Induced Cardiotoxicity

“…When using DOX as a chemotherapy agent, a common limiting factor is the development of potentially lethal heart failure, which typically occurs in a dose-dependent manner [ 44 ]. The increased chamber diameter and loss of cardiac dimensions reduce ejection fraction, typically resulting in the cessation of DOX administration and leaving the patient with a potentially serious heart condition [ 45 , 46 ]. The ability to preserve chamber diameter during DOX treatment could increase the duration and dose of DOX that can be used in clinical settings and/or improve patient outcomes.…”