title: Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction.
abstract: OBJECTIVE
  To investigate whether dimethyl sulfoxide (DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatory response syndrome and multiple organ dysfunction syndrome.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline (SS group); sham with administration of DMSO (SD group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group). Each group contained three subgroups according to 4 h, 8 h, and 24 h after surgery. At 4 h, 8 h, and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10] and oxides (myeloperoxidase, malonaldehyde, and superoxide dismutase) were examined. The levels of diamine oxidase (DAO) in plasma and intestinal mucosal blood flow (IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The intestinal epithelial tight junction protein, ZO-1, was observed by immunofluorescence.
  
  
  RESULTS
  DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration (P < 0.05). DMSO decreased the content of malondialdehyde (MDA) and increased the activity of superoxide dehydrogenase (SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group, respectively (P < 0.05). DMSO alleviated injury in intestinal villi, and the gut injury score was significantly lower than the ZS group (3.6 ± 0.2 vs 4.2 ± 0.3, P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS group (65.1 ± 4.7 U/L vs 81.1 ± 5.0 U/L, P < 0.05). DMSO significantly preserved ZO-1 protein expression and localization 24 h after zymosan administration. The TUNEL analysis indicated that the number of apoptotic intestinal cells in the ZS group was much higher than the ZD group (P < 0.05).
  
  
  CONCLUSIONS
  DMSO inhibited intestinal cytokines and protected against zymosan-induced gut barrier dysfunction.
authors.affiliation: Yu-Meng Li, Jin-Guang Zheng, Zeng-Kai Zhao, Jing-Yuan Li, Sen Hu, Laboratory for Shock and Multiple Organ Dysfunction of Burns Institute, Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Yu-Meng
authors.initials: YM
authors.lastname: Li
authors.affiliation: Yu-Meng Li, Jin-Guang Zheng, Zeng-Kai Zhao, Jing-Yuan Li, Sen Hu, Laboratory for Shock and Multiple Organ Dysfunction of Burns Institute, Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Yu-Meng Li, Jin-Guang Zheng, Zeng-Kai Zhao, Jing-Yuan Li, Sen Hu, Laboratory for Shock and Multiple Organ Dysfunction of Burns Institute, Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Jin-Guang
authors.initials: JG
authors.lastname: Zheng
authors.affiliation: Yu-Meng Li, Jin-Guang Zheng, Zeng-Kai Zhao, Jing-Yuan Li, Sen Hu, Laboratory for Shock and Multiple Organ Dysfunction of Burns Institute, Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Bai
authors.affiliation: Yu-Meng Li, Jin-Guang Zheng, Zeng-Kai Zhao, Jing-Yuan Li, Sen Hu, Laboratory for Shock and Multiple Organ Dysfunction of Burns Institute, Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Zeng-Kai
authors.initials: ZK
authors.lastname: Zhao
authors.affiliation: Yu-Meng Li, Jin-Guang Zheng, Zeng-Kai Zhao, Jing-Yuan Li, Sen Hu, Laboratory for Shock and Multiple Organ Dysfunction of Burns Institute, Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Li
authors.affiliation: Yu-Meng Li, Jin-Guang Zheng, Zeng-Kai Zhao, Jing-Yuan Li, Sen Hu, Laboratory for Shock and Multiple Organ Dysfunction of Burns Institute, Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Hu
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004751:Enteritis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009102:Multiple Organ Failure / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced; D019108:Tight Junctions / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D015054:Zymosan
chemical_list: D016166:Free Radical Scavengers; C569044:Tjp1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D016753:Interleukin-10; D008315:Malondialdehyde; D015054:Zymosan; D013482:Superoxide Dismutase; D006631:Amine Oxidase (Copper-Containing); D004121:Dimethyl Sulfoxide
keywords: Dimethyl sulfoxide; Inflammation; Intestinal barrier; Tight junction; Zymosan