title: Mitochondrial DNA-Induced Inflammatory Responses and Lung Injury in Thermal Injury Rat Model: Protective Effect of Epigallocatechin Gallate.
abstract: Lungs are easily damaged by the inflammatory responses induced after extensive burns. The aim here was to investigate the protective role of epigallocatechin gallate (EGCG) in mitochondrial DNA (mtDNA)-mediated inflammatory responses and acute respiratory distress syndrome (ARDS) in a rat model of thermal injury. Male Sprague-Dawley rats were randomly assigned to five groups. In the first experiment, a full-thickness thermal injury or control procedure, covering 30% of the TBSA, was inflicted on three groups designated as the thermal injury, EGCG, and sham control groups. In the second experiment, another two groups were established by transfusion with either mtDNA (mtDNA group) or phosphate-buffered saline (phosphate-buffered saline group). Blood samples and lung tissue from all five groups were collected and the plasma concentrations of mtDNA and inflammatory mediators were measured. Bronchoalveolar lavage fluid was collected and histological analysis of the lung tissue was performed to evaluate the severity of ARDS. Significant increases in mtDNA and inflammatory mediator plasma concentrations were seen in the thermal injury and EGCG groups when compared with controls (P < .05). The plasma concentrations of mtDNA and inflammatory mediators were significantly decreased after the administration of EGCG (P < .05). EGCG also significantly reduced the severity of acute lung injury (P < .05). Intravenous administration of mtDNA significantly increased concentrations of inflammatory mediators and caused severe ARDS (P < .05). Our results suggest that mtDNA is important for thermal injury-induced inflammation and associated ARDS. EGCG possesses anti-inflammatory and lung-protective properties, and might act by limiting mtDNA release after thermal injury.
authors.affiliation: From the *Department of Burns and Plastic Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China; †Department of Anesthesiology, Chengdu Women and Children's Central Hospital, People's Republic of China; and ‡West China School of Medicine, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Ruiqi
authors.initials: R
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Si
authors.initials: S
authors.lastname: Si
authors.forename: Xueshan
authors.initials: X
authors.lastname: Zhao
authors.forename: Siwei
authors.initials: S
authors.lastname: Bi
authors.forename: Ying
authors.initials: Y
authors.lastname: Cen
mesh_terms: D055371:Acute Lung Injury / Q000178:diet therapy*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D020011:Protective Agents; D002392:Catechin; C045651:epigallocatechin gallate