scholarly journals Simulated aeromedical evacuation exacerbates burn induced lung injury: targeting mitochondrial DNA for reversal

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Meng-Jing Xiao ◽  
Xiao-Fang Zou ◽  
Bin Li ◽  
Bao-Long Li ◽  
Shi-Jian Wu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Hypobaric Hypoxia ◽  
Dnase I ◽  
Treatment Intervention ◽  
Aeromedical Evacuation ◽  
Hypoxia Exposure ◽  
Histopathological Evaluation ◽  
Lung Injuries ◽  
Mda Content

Abstract Background Aeromedical evacuation of patients with burn trauma is an important transport method in times of peace and war, during which patients are exposed to prolonged periods of hypobaric hypoxia; however, the effects of such exposure on burn injuries, particularly on burn-induced lung injuries, are largely unexplored. This study aimed to determine the effects of hypobaric hypoxia on burn-induced lung injuries and to investigate the underlying mechanism using a rat burn model. Methods A total of 40 male Wistar rats were randomly divided into four groups (10 in each group): sham burn (SB) group, burn in normoxia condition (BN) group, burn in hypoxia condition (BH) group, and burn in hypoxia condition with treatment intervention (BHD) group. Rats with 30% total body surface area burns were exposed to hypobaric hypoxia (2000 m altitude simulation) or normoxia conditions for 4 h. Deoxyribonuclease I (DNase I) was administered systemically as a treatment intervention. Systemic inflammatory mediator and mitochondrial deoxyribonucleic acid (mtDNA) levels were determined. A histopathological evaluation was performed and the acute lung injury (ALI) score was determined. Malonaldehyde (MDA) content, myeloperoxidase (MPO) activity, and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome level were determined in lung tissues. Data among groups were compared using analysis of variance followed by Tukey’s test post hoc analysis. Results Burns resulted in a remarkably higher level of systemic inflammatory cytokines and mtDNA release, which was further heightened by hypobaric hypoxia exposure (P < 0.01). Moreover, hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression, MDA content, and MPO activity in the lung (P < 0.05 or P < 0.01). Burn-induced lung injuries were exacerbated, as shown by the histopathological evaluation and ALI score (P < 0.01). Administration of DNase I markedly reduced mtDNA release and systemic inflammatory cytokine production. Furthermore, the NLRP3 inflammasome level in lung tissues was decreased and burn-induced lung injury was ameliorated (P < 0.01). Conclusions Our results suggested that simulated aeromedical evacuation further increased burn-induced mtDNA release and exacerbated burn-induced inflammation and lung injury. DNase I reduced the release of mtDNA, limited mtDNA-induced systemic inflammation, and ameliorated burn-induced ALI. The intervening mtDNA level is thus a potential target to protect from burn-induced lung injury during aeromedical conditions and provides safer air evacuations for severely burned patients.

scholarly journals Simulated Aeromedical Evacuation Exacerbates Burn Induced Lung Injury: Targeting Mitochondrial DNA for Reversal

2020 ◽  
Author(s):  
Mengjing Xiao ◽  
Xiaofang Zou ◽  
Bin Li ◽  
Baolong Li ◽  
Shijian Wu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Hypobaric Hypoxia ◽  
Deoxyribonucleic Acid ◽  
Lung Injury Score ◽  
Myeloperoxidase Activity ◽  
Aeromedical Evacuation ◽  
Deoxyribonuclease I ◽  
Acid Release

Abstract Background: Aeromedical evacuation of patients with burn trauma is an important transport method at both wartime and peacetime, which exposes patients to prolonged periods of hypobaric hypoxia. However, the effects of such exposure on burn injury, particularly on burn induced lung injury are largely unexplored. The objective of this study is to investigate the effect of hypobaric hypoxia on burn induced lung injury and to discuss the possible mechanism by using a rat burn model. Methods: Male wistar rats inflicted with 30% total body surface area burn were exposed to hypobaric hypoxia condition (simulated 2000m altitude) or normoxia control for 24 h. Deoxyribonuclease I was systemically administrated as treatment intervention. Systemic inflammatory mediators and mitochondrial deoxyribonucleic acid level were detected. The histopathological examination, and acute lung injury score were determined. Malonaldehyde content, myeloperoxidase activity, and the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome level in the lung tissue were measured. Data among groups were compared by using analysis of variance followed by the post hoc analysis of Tukey's test. Results: Burn resulted in remarkably higher level of systemic inflammatory cytokines and mitochondrial deoxyribonucleic acid release, which was further heightened by hypobaric hypoxia exposure. Moreover, hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression, elevated malonaldehyde content and myeloperoxidase activity in the lung. Burn induced lung injury was exacerbated as shown by histopathological examination and acute lung injury score. Administration of deoxyribonuclease I markedly reduced mitochondrial deoxyribonucleic acid release and systemic inflammatory cytokines production. Furthermore, NLRP3 inflammasome level in the lung tissue was decreased and burn induced lung injury was ameliorated. Conclusions: Our results suggested that simulated aeromedical evacuation further increased the burn induced mitochondrial deoxyribonucleic acid release and exacerbated burn induced inflammation and lung injury. Deoxyribonuclease I reduced the release of mitochondrial deoxyribonucleic acid and limited the mitochondrial deoxyribonucleic acid-induced systemic inflammation, ameliorated burn-induced acute lung injury. Intervening mitochondrial deoxyribonucleic acid level could be a potential target to protect from burn-induced lung injury during aeromedical conditions and provide with safer air evacuations for severely burned patients.

scholarly journals SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pan Pan ◽  
Miaomiao Shen ◽  
Zhenyang Yu ◽  
Weiwei Ge ◽  
Keli Chen ◽  
...  
Keyword(s):  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Cultured Cells ◽  
Inflammatory Responses ◽  
Specific Inhibitor ◽  
Inflammasome Activation ◽  
N Protein ◽  
Distinct Mechanism ◽  
Nlrp3 Inflammasome Activation ◽  
Proinflammatory Responses

AbstractExcessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.

scholarly journals Tractotomy using the Penrose drain guide for deep lung injury caused by chest drainage: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hironori Oyamatsu ◽  
Hideki Tsubouchi ◽  
Kunio Narita
Keyword(s):  
Lung Injury ◽  
Chest Tube ◽  
Drain Tube ◽  
Chest Drainage ◽  
Respiratory Condition ◽  
Penrose Drain ◽  
Multiple Rib Fractures ◽  
Lung Injuries ◽  
The Right ◽  
Damaged Vessel

Abstract Background Pulmonary tractotomy effectively treats deep pulmonary penetrating injuries; however, it requires the accurate insertion of forceps or a stapler into the wound tract. This report describes a case of tractotomy using the Penrose drain guide for a deep lung injury caused by chest drainage. Case presentation A 75-year-old man suffered multiple rib fractures and hemothorax. After admission, chest tube drainage was performed because the patient’s respiratory condition deteriorated due to increased right pleural effusion. However, as the chest tube was stabbing into the right upper lobe, a pulmonary tractotomy was performed to treat the injury. Cutting the visceral pleura just over the tip of the chest tube caused the tube to completely penetrate the lung. A Penrose drain tube was fixed to the chest tube, which was then removed. The Penrose drain tube completely penetrated the lung and was coupled to the anvil side of the stapler to guide it smoothly into the wound tract. After stapling left the wound tract open, selective suture ligation of the damaged vessel and bronchioles was performed. Conclusions Although the indications for tractotomy using the Penrose drain guide are limited, we believe that this technique can be useful in patients with deep stabbing or penetrating lung injuries with rod- or tube-shaped foreign body remnants.

Vitamin E prevents hypobaric hypoxia-induced mitochondrial dysfunction in skeletal muscle

2007 ◽  
Vol 113 (12) ◽  
pp. 459-466 ◽  
Author(s):  
José Magalhães ◽  
Rita Ferreira ◽  
Maria J. Neuparth ◽  
Paulo J. Oliveira ◽  
Franklim Marques ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vitamin E ◽  
Mitochondrial Dysfunction ◽  
Hypobaric Hypoxia ◽  
Mitochondrial Membrane ◽  
Mitochondrial Protein ◽  
Membrane Integrity ◽  
Outer Mitochondrial Membrane ◽  
Hypoxia Exposure

In the present study, the effect of vitamin E (α-tocopherol) on mice skeletal muscle mitochondrial dysfunction and oxidative damage induced by an in vivo acute and severe hypobaric hypoxic insult (48 h at a barometric pressure equivalent to 8500 m) has been investigated. Male mice (n=24) were randomly divided into the following four groups (n=6): control (C), hypoxia (H), vitamin E (VE; 60 mg/kg of body weight intraperitoneally, three times/week for 3 weeks) and hypoxia+VE (HVE). A significant increase in mitochondrial protein CGs (carbonyl groups) was found in the H group compared with the C group. Confirming previous observations from our group, hypoxia induced mitochondrial dysfunction, as identified by altered respiratory parameters. Hypoxia exposure increased Bax content and decreased the Bcl-2/Bax ratio, whereas Bcl-2 remained unchanged. Inner and outer mitochondrial membrane integrity were significantly affected by hypoxia exposure; however, vitamin E treatment attenuated the effect of hypoxia on mitochondrial oxidative phosphorylation and on the levels of CGs. Vitamin E supplementation also prevented the Bax and Bcl-2/Bax ratio impairments caused by hypoxia, as well as the decrease in inner and outer mitochondrial membrane integrity. In conclusion, the results suggest that vitamin E prevents the loss of mitochondrial integrity and function, as well as the increase in Bax content, which suggests that mitochondria are involved in increased cell death induced by severe hypobaric hypoxia in mice skeletal muscle.

scholarly journals Pengaruh Paparan Hipoksia terhadap Aktivitas Antioksidan Katalase dan Kadar Malondialdehid (MDA) pada Jaringan Hati Tikus

Jurnal BIOMA ◽  
2014 ◽  
Vol 10 (2) ◽  
pp. 27
Author(s):  
Rini Puspitaningrum ◽  
Amanda Putri Lestari ◽  
Tri Murtiati
Keyword(s):  
Antioxidant Activity ◽  
Free Radicals ◽  
Cell Membrane ◽  
Rat Liver ◽  
Catalase Activity ◽  
Liver Tissue ◽  
Hypoxia Exposure ◽  
Randomized Design ◽  
Mda Content ◽  
Key Words Catalase

Abstract content in the tissue. Hypoxia can make the formation of free radicals or reactive oxygen species (ROS) which reactive to cell membrane. Body will avoid free radicals by producing antioxidant, such as catalase enzyme. The reaction between ROS and cell membrane will form malondialdehyde (MDA). Liver is the main location of catalase. This research was aimed to know the influence of hypoxia exposure toward catalase antioxidant activity and MDA content in the rat liver tissue. This research used experiment method with fully randomized design. Based on one way Anova test (p≤0.01), it was shown that there had no average difference on catalase activity and MDA content toward length hypoxia exposure. The conclusion of this research was no influence of hypoxia exposure toward catalase activity and MDA content in rat liver tissue.   Key words: catalase antioxidant activity, hypoxia, malondialdehyde (MDA) content,rat liver tissue

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