title: Pyruvate Is Superior to Citrate in Oral Rehydration Solution in the Protection of Intestine via Hypoxia-Inducible Factor-1 Activation in Rats With Burn Injury.
abstract: Recent studies have suggested that pyruvate-enriched oral rehydration solution (Pyr-ORS) may be superior to the standard bicarbonate-based ORS in the protection of intestine from ischemic injury. The aim of this study was to compare the effects of Pyr-ORS with citrate-enriched ORS (Cit-ORS) on the intestinal hypoxia-inducible factor-1 (HIF-1)-erythropoietin (EPO) signaling pathway for enteral rehydration in a rat model of burn injury.
  
  
  
  Rats were randomly assigned to 4 groups (N = 20, 2 subgroups each: n = 10): scald sham (group SS), scald with no fluid resuscitation (group SN), scald and resuscitation with enteral Cit-ORS (group SC), and scald and resuscitation with enteral Pyr-ORS (group SP). At 2.5 and 4.5 hours after a 35% total body surface area (TBSA) scald, intestinal mucosal blood flow (IMBF), contents of HIF-1, EPO, endothelial nitric oxide synthase (eNOS), nitric oxide (NO), barrier protein (ZO-1), levels of serum diamine oxidase (DAO), and intestinal mucosal histology injury score were determined.
  
  
  
  Serum DAO activities in the scalded groups were significantly elevated, but less raised in group SP than in group SC, at 2.5 hours and at 4.5 hours after the scald. Further, group SP more profoundly preserved intestinal HIF-1 expression compared with group SC at the 2 time points. Compared with group SC, group SP had markedly elevated intestinal EPO, eNOS, and NO levels at the same time points, respectively (P < .05). Similarly, IMBF and ZO-1 levels were significantly higher in group SP than in group SC. Intestinal mucosal histopathological scores were statistically higher at 2.5 hours and 4.5 hours after scalding but were more attenuated in group SP than in group SC (P < .05). Immunofluorescence expression of intestinal mucosal ZO-1 was consistent with the above changes. The above parameters were also significantly different between groups SC and SN (all P < .05).
  
  
  
  Pyr-ORS provides a superior option to Cit-ORS for the preservation of intestinal blood flow and barrier function and the attenuation of histopathological alterations in enteral resuscitation of rats with burn injury. Its underlying mechanism may be closely related to the pyruvate in activation of intestinal HIF-1-EPO signaling cascades.
authors: Key Research Laboratory of Tissue Repair and Regeneration of PLA and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China.
authors: Sen
authors: S
authors: Hu
authors: Key Research Laboratory of Tissue Repair and Regeneration of PLA and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China.
authors: Zhi-Long
authors: ZL
authors: Lin
authors: Medical School of Chinese PLA, Beijing, China.
authors: Zeng-Kai
authors: ZK
authors: Zhao
authors: Department of Burns and Plastic Surgery, The Fifth Hospital of Harbin, Harbin, Heilongjiang Province, China.
authors: Rui
authors: R
authors: Liu
authors: Department of Burns and Plastic Surgery, the Armed Police General Hospital of People's Liberation Army, Beijing, China.
authors: Li
authors: L
authors: Ma
authors: Key Research Laboratory of Tissue Repair and Regeneration of PLA and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China.
authors: Hong-Min
authors: HM
authors: Luo
authors: Fresenius Dialysis Centers at Chicago, Rolling Meadows, IL, USA Shanghai Sandai Pharmaceutical R&D Company, Pudong, Shanghai, China fqzh60130@yahoo.com.
authors: Fang-Qiang
authors: FQ
authors: Zhou
authors: Department of Burns and Plastic Surgery, the Armed Police General Hospital of People's Liberation Army, Beijing, China.
authors: Xiao-Dong
authors: XD
authors: Bai
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000097:blood / Q000235:genetics; D000818:Animals; D001639:Bicarbonates / Q000737:chemistry; D001830:Body Surface Area; D002056:Burns / Q000188:drug therapy*; D019343:Citric Acid / Q000008:administration & dosage*; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D005440:Fluid Therapy; D005947:Glucose / Q000737:chemistry; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D011189:Potassium Chloride / Q000737:chemistry; D019289:Pyruvic Acid / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D015398:Signal Transduction; D012965:Sodium Chloride / Q000737:chemistry; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D001639:Bicarbonates; D051793:Hypoxia-Inducible Factor 1; C569044:Tjp1 protein, rat; C044142:World Health Organization oral rehydration solution; D062826:Zonula Occludens-1 Protein; D004921:Erythropoietin; D019343:Citric Acid; D012965:Sodium Chloride; D011189:Potassium Chloride; D019289:Pyruvic Acid; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D006631:Amine Oxidase (Copper-Containing); D005947:Glucose
keywords: ZO-1; burns; erythropoietin; hypoxia inducible factor-1; intestinal mucosal blood flow; oral rehydration solution; pyruvate