title: Intestinal dipeptide absorption is preserved during thermal injury and cytokine treatment.
abstract: BACKGROUND
  Intestinal barrier function is impaired during thermal injury; however, the effects of thermal injury on the absorption of dietary peptides are not well characterized. The purpose of this study was to determine the impact of thermal injury on dipeptide absorption in rats and to describe the influence of inflammatory cytokines on the expression of the oligopeptide transporter PEPT1 and dipeptide permeability in cultured intestinal cells (Caco-2 cells).
  
  
  METHODS
  Sprague Dawley rats were assigned to 30% body surface area burn (n = 7) or sham (n = 8) groups. Twenty-four hours following burn/sham, the proximal jejunum was cannulated. The jejunal segment was perfused with buffer containing the dipeptide glycylsarcosine (Gly-Sar), and intestinal permeability (P(eff)) was calculated. For in vitro experiments, Caco-2 cells were grown on permeable supports and treated with tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 (10 ng/mL) alone and in combination for 48 hours. The effective apical-to-basolateral permeabilities (P(eff)) of Gly-Sar were measured, and PEPT1 expression was determined using reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Gly-Sar P(eff) was similar in burn and sham rats (6.67 +/- 2.27 x 10(-5) vs 7.58 +/- 2.20 x 10(-5) cm/s, respectively, P = .45). In Caco-2 cells, cytokine treatment did not alter PEPT1 expression (P = .954) or the P(eff) of Gly-Sar (P = .806).
  
  
  CONCLUSIONS
  Intestinal absorption of the dipeptide Gly-Sar is preserved 24 hours following thermal injury in rats. Likewise, PEPT1 expression and peptide absorption are preserved following treatment with TNF-alpha, IL-6, and IL-10 in Caco-2 monolayers. These findings imply that intestinal dipeptide absorption may be preserved during burn injury. This may lead to new strategies to optimize enteral protein delivery in burn patients.
authors.affiliation: Department of Pharmacy Practice, Purdue University School of Pharmacy and Pharmaceutical Sciences, Indianapolis, Indiana, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Foster
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Gonzales
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Amidon
authors.forename: Lynda S
authors.initials: LS
authors.lastname: Welage
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004151:Dipeptides / Q000493:pharmacokinetics*; D017097:Electric Impedance; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D000074011:Peptide Transporter 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004151:Dipeptides; D015850:Interleukin-6; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C004194:glycylsarcosine