title: Topically applied metal chelator reduces thermal injury progression in a rat model of brass comb burn.
abstract: Oxidative stress may be involved in the cellular damage and tissue destruction as burn wounds continues to progress after abatement of the initial insult. Since iron and calcium ions play key roles in oxidative stress, this study tested whether topical application of Livionex formulation (LF) lotion, that contains disodium EDTA as a metal chelator and methyl sulfonyl methane (MSM) as a permeability enhancer, would prevent or reduce burns.
  
  
  METHODS
  We used an established brass comb burn model with some modifications. Topical application of LF lotion was started 5 min post-burn, and repeated every 8 h for 3 consecutive days. Rats were euthanized and skin harvested for histochemistry and immunohistochemistry. Formation of protein adducts of 4-hydroxynonenal (HNE), malonadialdehyde (MDA) and acrolein (ACR) and expression of aldehyde dehydrogenase (ALDH) isozymes, ALDH1 and ALDH2 were assessed.
  
  
  RESULTS
  LF lotion-treated burn sites and interspaces showed mild morphological improvement compared to untreated burn sites. Furthermore, the lotion significantly decreased the immunostaining of lipid aldehyde-protein adducts including protein -HNE, -MDA and -ACR adducts, and restored the expression of aldehyde dehydrogenase isozymes in the unburned interspaces.
  
  
  CONCLUSIONS
  This data, for the first time, demonstrates that a topically applied EDTA-containing lotion protects burns progression with a concomitant decrease in the accumulation of reactive lipid aldehydes and protection of aldehyde dehydrogenase isozymes. Present studies are suggestive of therapeutic intervention of burns by this novel lotion.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647, United States.
authors.forename: Cheng Z
authors.initials: CZ
authors.lastname: Wang
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555-0647, United States; Shriners Hospital for Children, Galveston, TX, United States.
authors.forename: Amina El
authors.initials: AE
authors.lastname: Ayadi
authors.affiliation: University of Miami Miller School of Medicine, Miami, FL 33124, United States.
authors.forename: Juhi
authors.initials: J
authors.lastname: Goswamy
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555-0647, United States; Institute for Translational Sciences, Galveston, TX, United States; Shriners Hospital for Children, Galveston, TX, United States.
authors.forename: Celeste C
authors.initials: CC
authors.lastname: Finnerty
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555-0647, United States; Shriners Hospital for Children, Galveston, TX, United States.
authors.forename: Randy
authors.initials: R
authors.lastname: Mifflin
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555-0647, United States; Shriners Hospital for Children, Galveston, TX, United States.
authors.forename: Linda
authors.initials: L
authors.lastname: Sousse
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX 77555-0647, United States.
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647, United States.
authors.forename: John
authors.initials: J
authors.lastname: Papaconstantinou
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555-0647, United States; Shriners Hospital for Children, Galveston, TX, United States.
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647, United States. Electronic address: nansari@utmb.edu.
authors.forename: Naseem H
authors.initials: NH
authors.lastname: Ansari
mesh_terms: D000171:Acrolein / Q000378:metabolism; D000279:Administration, Cutaneous; D000444:Aldehyde Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D002056:Burns; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004195:Disease Models, Animal; D004492:Edetic Acid / Q000494:pharmacology*; D007150:Immunohistochemistry; D008315:Malondialdehyde / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D050697:Retinal Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013450:Sulfones / Q000494:pharmacology*; D015599:Trauma Severity Indices; D015032:Zinc
chemical_list: D000447:Aldehydes; D002614:Chelating Agents; D024101:Mitochondrial Proteins; D013450:Sulfones; C048399:brass; D008315:Malondialdehyde; D000171:Acrolein; D003300:Copper; D004492:Edetic Acid; C025910:dimethyl sulfone; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; C523119:Aldh1a1 protein, rat; D050697:Retinal Dehydrogenase; D015032:Zinc; C027576:4-hydroxy-2-nonenal; D004121:Dimethyl Sulfoxide
keywords: Brass comb burn; Burn progression; Iron chelation; Oxidative stress; Reactive aldehydes; Thermal injury; Wound healing