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

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.

• Authors: Jake J Wen, Taylor P Williams, Claire B Cummins, Kayla M Colvill, Geetha L Radhakrishnan, Ravi S Radhakrishnan
• Journal: Journal of the American College of Surgeons (J Am Coll Surg) Vol. 232 Issue 4 Pg. 642-655 (04 2021) ISSN: 1879-1190 [Electronic] United States
• PMID: 33421567 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• MitoTEMPO
• Organophosphorus Compounds
• Piperidines
• Reactive Oxygen Species

Topics

• Animals
• Antioxidants (administration & dosage)
• Burns (complications, therapy)
• Disease Models, Animal
• Echocardiography
• Heart (drug effects)
• Heart Failure (diagnosis, drug therapy, etiology, pathology)
• Humans
• Injections, Intraperitoneal
• Male
• Mitochondria (drug effects, pathology)
• Myocardium (cytology, pathology)
• Organophosphorus Compounds (administration & dosage)
• Piperidines (administration & dosage)
• Rats
• Reactive Oxygen Species (metabolism)