title: Time-Dependent and Organ-Specific Changes in Mitochondrial Function, Mitochondrial DNA Integrity, Oxidative Stress and Mononuclear Cell Infiltration in a Mouse Model of Burn Injury.
abstract: Severe thermal injury induces a pathophysiological response that affects most of the organs within the body; liver, heart, lung, skeletal muscle among others, with inflammation and hyper-metabolism as a hallmark of the post-burn damage. Oxidative stress has been implicated as a key component in development of inflammatory and metabolic responses induced by burn. The goal of the current study was to evaluate several critical mitochondrial functions in a mouse model of severe burn injury. Mitochondrial bioenergetics, measured by Extracellular Flux Analyzer, showed a time dependent, post-burn decrease in basal respiration and ATP-turnover but enhanced maximal respiratory capacity in mitochondria isolated from the liver and lung of animals subjected to burn injury. Moreover, we detected a tissue-specific degree of DNA damage, particularly of the mitochondrial DNA, with the most profound effect detected in lungs and hearts of mice subjected to burn injury. Increased mitochondrial biogenesis in lung tissue in response to burn injury was also observed. Burn injury also induced time dependent increases in oxidative stress (measured by amount of malondialdehyde) and neutrophil infiltration (measured by myeloperoxidase activity), particularly in lung and heart. Tissue mononuclear cell infiltration was also confirmed by immunohistochemistry. The amount of poly(ADP-ribose) polymers decreased in the liver, but increased in the heart in later time points after burn. All of these biochemical changes were also associated with histological alterations in all three organs studied. Finally, we detected a significant increase in mitochondrial DNA fragments circulating in the blood immediately post-burn. There was no evidence of systemic bacteremia, or the presence of bacterial DNA fragments at any time after burn injury. The majority of the measured parameters demonstrated a sustained elevation even at 20-40 days post injury suggesting a long-lasting effect of thermal injury on organ function. The current data show that there are marked time-dependent and tissue-specific alterations in mitochondrial function induced by thermal injury, and suggest that mitochondria-specific damage is one of the earliest responses to burn injury. Mitochondria may be potential therapeutic targets in the future experimental therapy of burns.
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, United States of America.|Shriners Hospitals for Children, Galveston, TX, United States of America.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Szczesny
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Attila
authors.initials: A
authors.lastname: Brunyánszki
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Akbar
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Gabor
authors.initials: G
authors.lastname: Oláh
authors.affiliation: Shriners Hospitals for Children, Galveston, TX, United States of America.|Department of Surgery, The University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Craig
authors.initials: C
authors.lastname: Porter
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, United States of America.|Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Tracy
authors.initials: T
authors.lastname: Toliver-Kinsky
authors.affiliation: Shriners Hospitals for Children, Galveston, TX, United States of America.|Department of Surgery, The University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: Labros
authors.initials: L
authors.lastname: Sidossis
authors.affiliation: Shriners Hospitals for Children, Galveston, TX, United States of America.|Department of Surgery, The University of Texas Medical Branch, Galveston, TX, United States of America.
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, United States of America.|Shriners Hospitals for Children, Galveston, TX, United States of America.
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabo
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism* / Q000473:pathology*; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004195:Disease Models, Animal; D004734:Energy Metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D008929:Mitochondria, Heart / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D009195:Peroxidase