4-hydroxy-2-nonenal and Burns

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.. 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.. 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.. 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.

Topics: Acrolein; Administration, Cutaneous; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Aldehyde Dehydrogenase, Mitochondrial; Aldehydes; Animals; Burns; Chelating Agents; Copper; Dimethyl Sulfoxide; Disease Models, Animal; Edetic Acid; Immunohistochemistry; Malondialdehyde; Mitochondrial Proteins; Oxidative Stress; Permeability; Rats; Retinal Dehydrogenase; Skin; Sulfones; Trauma Severity Indices; Zinc

Patients with severe burns are highly susceptible to bacterial infection. While immunosuppression facilitates infection, the contribution of soft tissues to infection beyond providing a portal for bacterial entry remains unclear. We showed previously that glutathione S-transferase S1 (gstS1), an enzyme with conjugating activity against the lipid peroxidation byproduct 4-hydroxynonenal (4HNE), is important for resistance against wound infection in Drosophila muscle. The importance of the mammalian functional counterpart of GstS1 in the context of wounds and infection has not been investigated. Here we demonstrate that the presence of a burn wound dramatically affects expression of both human (hGSTA4) and mouse (mGsta4) 4HNE scavengers. hGSTA4 is down-regulated significantly within 1 wk of thermal burn injury in the muscle and fat tissues of patients from the large-scale collaborative Inflammation and the Host Response to Injury multicentered study. Similarly, mGsta4, the murine GST with the highest catalytic efficiency for 4HNE, is down-regulated to approximately half of normal levels in mouse muscle immediately postburn. Consequently, 4HNE protein adducts are increased 4- to 5-fold in mouse muscle postburn. Using an open wound infection model, we show that deletion of mGsta4 renders mice more susceptible to infection with the prevalent wound pathogen Pseudomonas aeruginosa, while muscle hGSTA4 expression negatively correlates with burn wound infection episodes per patient. Our data suggest that hGSTA4 down-regulation and the concomitant increase in 4HNE adducts in human muscle are indicative of susceptibility to infection in individuals with severely thermal injuries.

Topics: Aldehydes; Animals; Bacterial Infections; Base Sequence; Burns; Case-Control Studies; Disease Models, Animal; Disease Susceptibility; DNA Primers; Down-Regulation; Female; Glutathione Transferase; Humans; Longitudinal Studies; Mice; Mice, 129 Strain; Mice, Knockout; Muscle, Skeletal; Prospective Studies; Pseudomonas Infections; Wound Infection