@article{0ef6ffde96b9406492efad8504779929,
title = "Metal chelation attenuates oxidative stress, inflammation, and vertical burn progression in a porcine brass comb burn model",
abstract = "Oxidative stress and inflammation may mediate cellular damage and tissue destruction as the burn wound continues to progress after the abatement of the initial insult. Since iron and calcium ions play key roles in oxidative stress, this study tested whether topical application of a metal chelator proprietary lotion (Livionex Formulation (LF) lotion), that contains disodium EDTA as a metal chelator and methyl sulfonyl methane (MSM) as a permeability enhancer, would prevent progression or reduce burn wound severity in a porcine model. We have reported earlier that in a rat burn model, LF lotion reduces thermal injury progression. Here, we used the porcine brass comb burn model that closely mimics the human condition for contact burns and applied LF lotion every 8 h starting 15 min after the injury. We found that LF lotion reduces the depth of cell death as assessed by TUNEL staining and blood vessel blockage in the treated burn sites and interspaces. The protein expression of pro-inflammatory markers IL-6, TNF-a, and TNFα Converting Enzyme (TACE), and lipid aldehyde production (protein-HNE) was reduced with LF treatment. LF lotion reversed the burn-induced decrease in the aldehyde dehydrogenase (ALDH-1) expression in the burn sites and interspaces. These data show that a topically applied EDTA-containing lotion protects both vertical and horizontal burn progression when applied after thermal injury. Curbing burn wound conversion and halting the progression of second partial burn to third-degree full-thickness burn remains challenging when it comes to burn treatment strategies during the acute phase. Burn wound conversion can be reduced with targeted treatments to attenuate the oxidative and inflammatory response in the immediate aftermath of the injury. Our studies suggest that LF lotion could be such a targeted treatment.",
keywords = "Burn conversion, Epithelial and endothelial cell death, Iron chelation, Oxidative damage, Thermal injury, Wound healing",
author = "{El Ayadi}, Amina and Salsbury, {John R.} and Perenlei Enkhbaatar and David Herndon and Naseem Ansari",
note = "Funding Information: The authors are grateful to Dr. Cheng Z. Wang for his help with the design, execution, and data collection for these studies. We also would like to thank Dr. San F. Yang for her technical assistance. This work was supported by grants from Livionex (Flow through NIH SBIR Phase I), NIAMS ( R43 AR062419 ) and by the Army, Navy, NIH , Air Force, VA , and Health Affairs to support the AFIRM II effort, under Award No. W81XWH-13-2-0054 . The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. This work was also supported in part by the NIEHS Center Grant P30 ES006676 (NA), and Shriners Hospital for Children grants 84202 (AE) and 80500 (DNH). We acknowledge the service received from the Histopathology Core Facility. None of the study sponsors had any role in the study design; the collection, analysis, or interpretation of data; the writing of the report; or in the decision to submit the article for publication. Funding Information: The authors are grateful to Dr. Cheng Z. Wang for his help with the design, execution, and data collection for these studies. We also would like to thank Dr. San F. Yang for her technical assistance. This work was supported by grants from Livionex (Flow through NIH SBIR Phase I), NIAMS (R43 AR062419) and by the Army, Navy, NIH, Air Force, VA, and Health Affairs to support the AFIRM II effort, under Award No. W81XWH-13-2-0054. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. This work was also supported in part by the NIEHS Center Grant P30 ES006676 (NA), and Shriners Hospital for Children grants 84202 (AE) and 80500 (DNH). We acknowledge the service received from the Histopathology Core Facility. None of the study sponsors had any role in the study design; the collection, analysis, or interpretation of data; the writing of the report; or in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = sep,
doi = "10.1016/j.redox.2021.102034",
language = "English (US)",
volume = "45",
journal = "Redox Biology",
issn = "2213-2317",
publisher = "Elsevier BV",
}