Effect of Mitochondrial Antioxidant (Mito-TEMPO) on Burn Injury-Induced Cardiac Dysfunction.

BACKGROUND: Imbalance of oxidants/antioxidants results in heart failure, contributing to mortality after burn injury. Cardiac mitochondria are a prime source of ROS, and a mitochondrial-specific antioxidant may improve burn-induced cardiomyopathy. We hypothesize that the mitochondrial-specific antioxidant, Mito-TEMPO, could protect cardiac function after burn.

STUDY DESIGN: Male rats had a 60% TBSA scald burn injury and were treated with/without Mito-TEMPO (7 mg·kg-1, ip) and harvested at 24 hours post burn. Echocardiography (ECHO) was employed for measurement of heart function. Masson Trichrome and H & E staining were used for cardiac fibrosis and immune response. O2K system assessed mitochondria function in vivo. 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 ETC-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: Mitochondrial-specific antioxidant (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.