Effect of Mitochondrial Antioxidant (Mito-TEMPO) on Burn-Induced Cardiac Dysfunction
- 7 January 2021
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American College of Surgeons
- Vol. 232 (4), 642-655
- https://doi.org/10.1016/j.jamcollsurg.2020.11.031
Abstract
Background Imbalance of oxidants/antioxidants results in heart failure, contributing to mortality after burn injury. Cardiac mitochondria are a prime source of reactive oxygen species (ROS), and a mitochondrial-specific antioxidant may improve burn-induced cardiomyopathy. We hypothesize that the mitochondrial-specific antioxidant, Triphenylphosphonium chloride (Mito-TEMPO), could protect cardiac function after burn. Study design Male rats had a 60% total body surface area (TBSA) scald burn injury and were treated with/without Mito-TEMPO (7 mg/kg-1, intraperitoneal) and harvested at 24 hours post-burn. Echocardiography (ECHO) was used for measurement of heart function. Masson Trichrome and hematoxylin and eosin (H & E) staining were used for cardiac fibrosis and immune response. Qualitative polymerase chain reaction (qPCR) was used for mitochondrial DNA replication and gene expression. Results Burn-induced cardiac dysfunction, fibrosis, and mitochondrial damage were assessed by measurement of mitochondrial function, DNA replication, and DNA-encoded electron transport chain-related gene expression. Mito-TEMPO partially improved the abnormal parameters. Burn-induced cardiac dysfunction was associated with crosstalk between the NFE2L2-ARE pathway, PDE5A-PKG pathway, PARP1-POLG-mtDNA replication pathway, and mitochondrial SIRT signaling. Conclusions Mito-TEMPO reversed burn-induced cardiac dysfunction by rescuing cardiac mitochondrial dysfunction. Mitochondria-targeted antioxidants may be an effective therapy for burn-induced cardiac dysfunction.Keywords
Funding Information
- University of Texas Medical Branch at Galveston
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