Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model

Amina El Ayadi; Cheng Z Wang; Min Zhang; Michael Wetzel; Anesh Prasai; Celeste C Finnerty; Perenlei Enkhbaatar; David N Herndon; Naseem H Ansari

doi:10.1093/burnst/tkaa024

您当前的位置：

首页 >

文章列表页 >

Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model

更新时间：2022-06-09

- Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model
- Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model
- Burns & Trauma 2020年8卷第1期
- 作者机构：
  
  1. Department of Surgery, University of Texas Medical Branch
  2. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch
  3. Department of Anesthesiology, University Blvd301., University of Texas Medical Branch
- 作者简介：
- 基金信息：
  
  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 US 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. Support was also provided, in part, by National Institute of Environmental Health Sciences (P30 ES006676), National Institute of General Medical Sciences (P50 GM060338 to DNH and R01 GM112936 to CCF) and Shriners Hospitals for Children (84202 to AE and 80500 to DNH). None of the study sponsors had any role in the study design;in the collection, analysis or interpretation of the data;in the writing of the report;or in the decision to submit the article for publication.
- DOI：10.1093/burnst/tkaa024
  中图分类号：
- 纸质出版日期：2020，
  
  网络出版日期：2020-10-2，
扫描看全文
Amina El Ayadi, Cheng Z Wang, Min Zhang, 等. Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model[J]. Burns & Trauma, 2020,8(1).

Amina El Ayadi, Cheng Z Wang, Min Zhang, Michael Wetzel, Anesh Prasai, Celeste C Finnerty, Perenlei Enkhbaatar, David N Herndon, Naseem H Ansari, Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model, Burns & Trauma, Volume 8, 2020, tkaa024, https://doi.org/10.1093/burnst/tkaa024
Amina El Ayadi, Cheng Z Wang, Min Zhang, 等. Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model[J]. Burns & Trauma, 2020,8(1). DOI： 10.1093/burnst/tkaa024.

Amina El Ayadi, Cheng Z Wang, Min Zhang, Michael Wetzel, Anesh Prasai, Celeste C Finnerty, Perenlei Enkhbaatar, David N Herndon, Naseem H Ansari, Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model, Burns & Trauma, Volume 8, 2020, tkaa024, https://doi.org/10.1093/burnst/tkaa024 DOI：

摘要

Abstract

BackgroundOne of the most pervasive complications of burn injury is wound progression

characterized by continuous tissue destruction in untreated wounds

which leads to wound infection

inflammation

oxidative stress and excessive scar formation. We determined whether additional tissue destruction could be attenuated with Livionex formulation (LF) lotion

which contains a metal-chelating agent and reduces inflammation in burn wounds.MethodsWe subjected male Sprague Dawley rats to a 2% total body surface area (TBSA) burn using a brass comb model and topically applied LF lotion (containing ethylenediaminetetraacetic acid and methyl sulfonyl methane) to the affected area every 8 hours over 3 days. Inflammatory cytokine levels

cell apoptosis and wound healing were compared in LF lotion-treated and untreated rats. Statistical analysis was performed using a one-way analysis of variance in conjunction with Tukey’s post-hoc test.ResultsSerum inflammatory cytokines were not detectable after 3 days

suggesting that small burn wounds induce only an immediate

localized inflammatory response. Microscopy revealed that LF lotion improved burn site pathology. Deoxynucleotidyl transferase biotin-d-UTP nick-end labeling staining showed reduced cell death in the LF-treated samples. LF lotion prevented the spread of tissue damage

as seen by increased amounts of Ki-67-positive nuclei in the adjacent epidermis and hair follicles. Tumor necrosis factor-alpha

interleukin-6 and inducible nitric oxide synthase levels in LF-treated skin sections from burned rats were comparable to the levels observed in unburned control sections

indicating that LF lotion reduces inflammation in and around the burn site.ConclusionsThese results establish LF lotion as a therapeutic agent for reducing inflammatory stress

cell death and tissue destruction when applied immediately after a burn injury. Further studies of LF lotion on large TBSA burns will determine its efficacy as an emergency treatment for reducing long-term morbidity and scarring.

关键词

Keywords

Burn progressionCytokinesOxidative stressCell deathWound healingInflammationMetal chelationskin

references

1.Peden M, McGee K, Sharma G. The injury chart book: a graphical overview of the global burden of injuries. Geneva, World Health Organization, 2002.

2.Brigham PA, McLoughlin E. Burn incidence and medical care use in the United States: estimates, trends, and data sources. J Burn Care Rehabil. 1996;17:95–107.

3.Church D, Elsayed S, Reid O, Winston B, Lindsay R. Burn wound infections. Clin Microbiol Rev. 2006;19:403–34.

4.Jackson DM. The treatment of burns: an exercise in emergency surgery. Ann R Coll Surg Engl. 1953;13:236–57.

5.Jackson DM. Diagnosis in the management of burns. Br Med J. 1959;1:1263–7.

6.Shupp JW, Nasabzadeh TJ, Rosenthal DS, Jordan MH, Fidler P, Jeng JC. A review of the local pathophysiologic bases of burn wound progression. J Burn Care Res. 2010;31:849–73.

7.El Ayadi A, Jay JW, Prasai A. Current approaches targeting the wound healing phases to attenuate fibrosis and scarring. Int J Mol Sci. 2020;21:1105.

8.Singh V, Devgan L, Bhat S, Milner SM. The pathogenesis of burn wound conversion. Ann Plast Surg. 2007;59:109–15.

9.Horton JW. Free radicals and lipid peroxidation mediated injury in burn trauma: the role of antioxidant therapy. Toxicology. 2003;189:75–88.

10.Parihar A, Parihar MS, Milner S, Bhat S. Oxidative stress and anti-oxidative mobilization in burn injury. Burns. 2008;34:6–17.

11.Schmauss D, Rezaeian F, Finck T, Machens HG, Wettstein R, Harder Y. Treatment of secondary burn wound progression in contact burns-a systematic review of experimental approaches. J Burn Care Res. 2015;36:e176–89.

12.Choi M, Ehrlich HP. U75412E, a lazaroid, prevents progressive burn ischemia in a rat burn model. Am J Pathol. 1993;142:519–28.

13.Fazal N, Al-Ghoul WM, Choudhry MA, Sayeed MM. PAF receptor antagonist modulates neutrophil responses with thermal injury in vivo. Am J Physiol Cell Physiol. 2001;281:C1310–7.

14.Singer AJ, Huang SS, Huang JS, McClain SA, Romanov A, Rooney J, et al. A novel TGF-beta antagonist speeds reepithelialization and reduces scarring of partial thickness porcine burns. J Burn Care Res. 2009;30:329–34.

15.Tobalem M, Harder Y, Rezaeian F, Wettstein R. Secondary burn progression decreased by erythropoietin. Crit Care Med. 2013;41:963–71.

16.Tobalem M, Harder Y, Schuster T, Rezaeian F, Wettstein R. Erythropoietin in the prevention of experimental burn progression. Br J Surg. 2012;99:1295–303.

17.Gauglitz GG, Song J, Herndon DN, Finnerty CC, Boehning D, Barral JM, et al. Characterization of the inflammatory response during acute and post-acute phases after severe burn. Shock. 2008;30:503–7.

18.Cetinkale O, Belce A, Konukoglu D, Senyuva C, Gumustas MK, Tas T. Evaluation of lipid peroxidation and total antioxidant status in plasma of rats following thermal injury. Burns. 1997;23:114–6.

19.Haycock JW, Ralston DR, Morris B, Freedlander E, MacNeil S. Oxidative damage to protein and alterations to antioxidant levels in human cutaneous thermal injury. Burns. 1997;23:533–40.

20.Hosnuter M, Gurel A, Babuccu O, Armutcu F, Kargi E, Isikdemir A. The effect of CAPE on lipid peroxidation and nitric oxide levels in the plasma of rats following thermal injury. Burns. 2004;30:21–5.

21.Schneider C, Porter NA, Brash AR. Routes to 4-hydroxynonenal: fundamental issues in the mechanisms of lipid peroxidation. J Biol Chem. 2008;283:15539–43.

22.Gueraud F, Atalay M, Bresgen N, Cipak A, Eckl PM, Huc L, et al. Chemistry and biochemistry of lipid peroxidation products. Free Radic Res. 2010;44:1098–124.

23.Niki E. Biomarkers of lipid peroxidation in clinical material. Biochimica et Biophysica Acta (BBA) – General Subjects. 2014;1840:809–17.

24.Negre-Salvayre A, Auge N, Ayala V, Basaga H, Boada J, Brenke R, et al. Pathological aspects of lipid peroxidation. Free Radic Res. 2010;44:1125–71.

25.Lee SE, Park YS. Role of lipid peroxidation-derived alpha, beta-unsaturated aldehydes in vascular dysfunction. Oxid Med Cell Longev. 2013. doi: 10.1155/2013/629028.

26.Welch KD, Davis TZ, Van Eden ME, Aust SD. Deleterious iron-mediated oxidation of biomolecules. Free Radic Biol Med. 2002;32:577–83.

27.Jones CM, Burkitt MJ. EPR spin-trapping evidence for the direct, one-electron reduction of tert-butylhydroperoxide to the tert-butoxyl radical by copper(II): paradigm for a previously overlooked reaction in the initiation of lipid peroxidation. J Am Chem Soc. 2003;125:6946–54.

28.Cheng Z, Li Y. What is responsible for the initiating chemistry of iron-mediated lipid peroxidation: an update. Chem Rev. 2007;107:748–66.

29.Liu P, Zhang M, Shoeb M, Hogan D, Tang L, Syed MF, et al. Metal chelator combined with permeability enhancer ameliorates oxidative stress-associated neurodegeneration in rat eyes with elevated intraocular pressure. Free Radic Biol Med. 2014;69:289–99.

30.Shoeb M, Zhang M, Xiao T, Syed MF, Ansari NH. Amelioration of endotoxin-induced inflammatory toxic response by a metal Chelator in rat eyes. Invest Ophthalmol Vis Sci. 2018;59:31–8.

31.Zhang M, Shoeb M, Liu P, Xiao T, Hogan D, Wong IG, et al. Topical metal chelation therapy ameliorates oxidation-induced toxicity in diabetic cataract. J Toxicol Environ Health A. 2011;74:380–91.

32.Wang CZ, Ayadi AE, Goswamy J, Finnerty CC, Mifflin R, Sousse L, et al. Topically applied metal chelator reduces thermal injury progression in a rat model of brass comb burn. Burns. 2015;41:1775–87.

33.Regas FC, Ehrlich HP. Elucidating the vascular response to burns with a new rat model. J Trauma. 1992;32:557–63.

34.Singer AJ, Berruti L, Thode HC Jr, McClain SA. Standardized burn model using a multiparametric histologic analysis of burn depth. Acad Emerg Med. 2000;7:1–6.

35.Wang CZ, Johnson KM. The role of caspase-3 activation in phencyclidine-induced neuronal death in postnatal rats. Neuropsychopharmacology. 2007;32:1178–94.

36.Gouma E, Simos Y, Verginadis I, Lykoudis E, Evangelou A, Karkabounas S. A simple procedure for estimation of total body surface area and determination of a new value of Meeh's constant in rats. Lab Anim. 2012;46:40–5.

37.Ueyama M, Maruyama I, Osame M, Sawada Y. Marked increase in plasma interleukin-6 in burn patients. J Lab Clin Med. 1992;120:693–8.

38.Poranki D, Goodwin C, Van Dyke M. Assessment of deep partial thickness burn treatment with keratin biomaterial hydrogels in a swine model. Biomed Res Int. 2016. https://doi.org/10.1155/2016/1803912.

39.Oksuz S, Ulkur E, Oncul O, Kose GT, Kucukodaci Z, Urhan M. The effect of subcutaneous mesenchymal stem cell injection on statis zone and apoptosis in an experimental burn model. Plast Reconstr Surg. 2013;131:463–71.

40.Abbas OL, Ozatik O, Gonen ZB, Ogut S, Entok E, Ozatik FY, et al. Prevention of burn wound progression by Mesenchymal stem cell transplantation: deeper insights into underlying mechanisms. Ann Plast Surg. 2018;81:715–24.

41.Rizzo JA, Burgess P, Cartie RJ, Prasad BM. Moderate systemic hypothermia decreases burn depth progression. Burns. 2013;39:436–44.

42.Zawacki BE. Reversal of capillary stasis and prevention of necrosis in burns. Ann Surg. 1974;180:98–102.

43.Hirth D, McClain SA, Singer AJ, Clark RA. Endothelial necrosis at 1 hour postburn predicts progression of tissue injury. Wound Repair Regen. 2013;21:563–70.

44.Tan JQ, Zhang HH, Lei ZJ, Ren P, Deng C, Li XY, et al. The roles of autophagy and apoptosis in burn wound progression in rats. Burns. 2013;39:1551–6.

45.Singer AJ, McClain SA, Taira BR, Guerriero JL, Zong W. Apoptosis and necrosis in the ischemic zone adjacent to third degree burns. Acad Emerg Med. 2008;15:549–54.

46.Salibian AA, Rosario ATD, Severo LAM, Nguyen L, Banyard DA, Toranto JD, et al. Current concepts on burn wound conversion-a review of recent advances in understanding the secondary progressions of burns. Burns. 2016;42:1025–35.

47.Corda S, Laplace C, Vicaut E, Duranteau J. Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. Am J Respir Cell Mol Biol. 2001;24:762–8.

48.Kim JJ, Lee SB, Park JK, Yoo YD. TNF-alpha-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-X(L). Cell Death Differ. 2010;17:1420–34.

49.Shoji Y, Uedono Y, Ishikura H, Takeyama N, Tanaka T. DNA damage induced by tumour necrosis factor-alpha in L929 cells is mediated by mitochondrial oxygen radical formation. Immunology. 1995;84:543–8.

50.Abdul-Muneer PM, Chandra N, Haorah J. Interactions of oxidative stress and neurovascular inflammation in the pathogenesis of traumatic brain injury. Mol Neurobiol. 2015;51:966–79.

51.Ansari NH, Wang L, Srivastava SK. Role of lipid aldehydes in cataractogenesis: 4-hydroxynonenal-induced cataract. Biochem Mol Med. 1996;58:25–30.

52.Choudhary S, Xiao T, Srivastava S, Zhang W, Chan LL, Vergara LA, et al. Toxicity and detoxification of lipid-derived aldehydes in cultured retinal pigmented epithelial cells. Toxicol Appl Pharmacol. 2005;204:122–34.

53.Choudhary S, Xiao T, Vergara LA, Srivastava S, Nees D, Piatigorsky J, et al. Role of aldehyde dehydrogenase isozymes in the defense of rat lens and human lens epithelial cells against oxidative stress. Invest Ophthalmol Vis Sci. 2005;46:259–67.

54.Zhang M, Shoeb M, Goswamy J, Liu P, Xiao TL, Hogan D, et al. Overexpression of aldehyde dehydrogenase 1A1 reduces oxidation-induced toxicity in SH-SY5Y neuroblastoma cells. J Neurosci Res. 2010;88:686–94.

查看原文

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

Betulinic acid accelerates diabetic wound healing by modulating hyperglycemia-induced oxidative stress, inflammation and glucose intolerance

The molecular mechanisms supporting the homeostasis and activation of dendritic epidermal T cell and its role in promoting wound healing

Pterostilbene accelerates wound healing by modulating diabetes-induced estrogen receptor β suppression in hematopoietic stem cells

Tailored biomedical materials for wound healing

Role of inflammation in neurological damage and regeneration following spinal cord injury and its therapeutic implications