Oral glutamine enhances heat shock protein expression and improves survival following hyperthermia.
No pharmacologic agent has shown benefit in treating heatstroke. Previous data indicate that enhanced heat shock protein 70 (HSP-70) expression can improve survival postexperimental heatstroke. Glutamine (GLN) can enhance HSP-70 expression in other injury models. This study assessed if orally administered GLN could enhance tissue HSP expression and could improve survival following whole body hyperthermia. Intestinal permeability and plasma endotoxin were assayed to determine if enhanced HSP expression correlated with improved organ function. GLN (0.65 g/kg) or an iso-nitrogenous control (Travasol; T) was given to rats via gavage twice daily for 5 days pre-heatstroke. Hyperthermia was performed in anesthetized rats by heating animals to 42 degrees C (rectal temperature) for 30 min. HSP-70 analyzed via Western blot. Gut permeability was measured 6 and 24 h post-hyperthermia. Plasma endotoxin was measured 24 h post-hyperthermia. Survival was analyzed for 5 days post-hyperthermia. GLN administration enhanced gut and lung HSP-70 post-hyperthermia. GLN administration led to significantly enhanced gut heat shock factor 1 (HSF-1) activation before heatstroke and at 1 h postheat stress. GLN decreased gut permeability at 6 and 24 h post-hyperthermia versus T. Plasma endotoxin also decreased in GLN-treated rats 24 h post-hyperthermia. Oral GLN therapy significantly improved survival (P < 0.05). Our results indicate that oral GLN can enhance tissue HSP-70 and HSF-1 activation post-hyperthermia. These results also indicate that enhanced HSP-70 may have functional significance as GLN-treated animals had decreased gut permeability, plasma endotoxin, and improve survival following lethal hyperthermia. Enhanced expression of HSP-70 may be an important mechanism leading to enhanced survival via GLN. These data indicate that oral GLN may useful in prevention of mortality from heatstroke in at risk populations.
Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Kristen D
KD
Singleton
Paul E
PE
Wischmeyer
D000284:Administration, Oral; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005334:Fever / Q000378:metabolism*; D005973:Glutamine / Q000008:administration & dosage / Q000627:therapeutic use*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D018883:Heat Stroke / Q000188:drug therapy*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000503:physiopathology; D010539:Permeability; D051381:Rats; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D005973:Glutamine