title: EICOSAPENTAENOIC ACID ENHANCES HEATSTROKE-IMPAIRED INTESTINAL EPITHELIAL BARRIER FUNCTION IN RATS.
abstract: OBJECTIVE
  Dysfunction of the intestinal barrier plays an important role in the pathological process of heatstroke. Omega-3 (or n-3) polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), help protect the intestinal mucosal barrier. This study assessed if pretreating rats with EPA or DHA could alleviate heat stress-induced damage to the intestinal barrier caused by experimental heatstroke.
  
  
  METHODS
  Male Wistar rats were pregavaged with either EPA, DHA, corn oil, or normal saline (all 1 g/kg) for 21 days before the heatstroke experiment (control rats were not exposed to heat). Experimental rats were exposed to an ambient temperature of 37°C and 60% humidity to induce heatstroke, and then they were allowed to recover at room temperature after rapid cooling. Survival time of rats was monitored after heatstroke. Horseradish peroxidase flux from the gut lumen and the level of plasma D-lactate were measured to analyze intestinal permeability at 6 h after heatstroke. Plasma endotoxin levels were determined using a limulus amoebocyte lysate assay. Expressions of the tight junction (TJ) proteins occludin and ZO-1 were analyzed by Western blot and localized by immunofluorescence microscopy. Tight junction protein morphology was observed by transmission electron microscopy. Fatty acids of ileal mucosa were analyzed using gas chromatography-mass selective detector.
  
  
  RESULTS
  Eicosapentaenoic acid significantly increased survival time after heatstroke. Eicosapentaenoic acid significantly decreased intestinal permeability and plasma endotoxin levels. Eicosapentaenoic acid effectively attenuated the heatstroke-induced disruption of the intestinal structure and improved the histology score, whereas DHA was less effective, and corn oil was ineffective. Pretreatment with EPA also increased expression of occludin and ZO-1 to effectively prevent TJ disruption. Eicosapentaenoic acid pretreatment enriched itself in the membrane of intestinal cells.
  
  
  CONCLUSIONS
  Our results indicate that EPA pretreatment is more effective than DHA pretreatment in attenuating heat-induced intestinal dysfunction and preventing TJ damage. Enhanced expression of TJ proteins that support the epithelial barrier integrity may be important for maintaining a functional intestinal barrier during heatstroke.
authors.affiliation: *Key Laboratory of Hot Zone Trauma Care and Tissue Repair of PLA, Department of Nutrition, General Hospital of Guangzhou Military Command †Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University ‡Key Laboratory of Hot Zone Trauma Care and Tissue Repair of PLA, Department of Intensive Care Unit, General Hospital of Guangzhou Military Command, Guangzhou, China.
authors.forename: Guizhen
authors.initials: G
authors.lastname: Xiao
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yuan
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Qiu
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Liu
authors.forename: Jiefu
authors.initials: J
authors.lastname: Lu
authors.forename: Liqun
authors.initials: L
authors.lastname: Tang
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Su
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D004731:Endotoxins / Q000097:blood; D005227:Fatty Acids / Q000378:metabolism; D018883:Heat Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007082:Ileum / Q000648:ultrastructure; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008297:Male; D008854:Microscopy, Electron; D010539:Permeability / Q000187:drug effects; D017208:Rats, Wistar; D062725:Tight Junction Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D004731:Endotoxins; D005227:Fatty Acids; D062725:Tight Junction Proteins; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid