title: Sodium butyrate protects against severe burn-induced remote acute lung injury in rats.
abstract: High-mobility group box 1 protein (HMGB1), a ubiquitous nuclear protein, drives proinflammatory responses when released extracellularly. It plays a key role as a distal mediator in the development of acute lung injury (ALI). Sodium butyrate, an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1 expression. This study investigates the effect of sodium butyrate on burn-induced lung injury. Sprague-Dawley rats were divided into three groups: 1) sham group, sham burn treatment; 2) burn group, third-degree burns over 30% total body surface area (TBSA) with lactated Ringer's solution for resuscitation; 3) burn plus sodium butyrate group, third-degree burns over 30% TBSA with lactated Ringer's solution containing sodium butyrate for resuscitation. The burned animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was assessed in terms of histologic changes and wet weight to dry weight (W/D) ratio. Tumor necrosis factor (TNF)-α and interleukin (IL)-8 protein concentrations in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme-linked immunosorbent assay, and HMGB1 expression in the lung was determined by Western blot analysis. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to reflect neutrophil infiltration and oxidative stress in the lung, respectively. As a result, sodium butyrate significantly inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and improved the pulmonary histologic changes induced by burn trauma. Furthermore, sodium butyrate administration decreased the TNF-α and IL-8 concentrations in BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs after severe burn. These results suggest that sodium butyrate attenuates inflammatory responses, neutrophil infiltration, and oxidative stress in the lungs, and protects against remote ALI induced by severe burn, which is associated with inhibiting HMGB1 expression.
authors.affiliation: Department of Burns, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: Xun
authors.initials: X
authors.lastname: Liang
authors.forename: Ren-Su
authors.initials: RS
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Ye-Xiang
authors.initials: YX
authors.lastname: Sun
authors.forename: Xu-Lin
authors.initials: XL
authors.lastname: Chen
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020148:Butyric Acid / Q000494:pharmacology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007377:Interleukin-3 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D007377:Interleukin-3; D016209:Interleukin-8; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C404145:myelopoietin; D020148:Butyric Acid; D016179:Granulocyte Colony-Stimulating Factor; D008315:Malondialdehyde; D009195:Peroxidase