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Intestinal Dipeptide Absorption Is Preserved During Thermal Injury and Cytokine Treatment

From the ¹ Department of Pharmacy Practice, Purdue University School of Pharmacy and Pharmaceutical Sciences, Indianapolis, Indiana; ² Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland;³ Department of Pharmaceutical Sciences, University of Michigan, College of Pharmacy, Ann Arbor, Michigan;⁴ Department of Clinical, Social and Administrative Sciences, University of Michigan College of Pharmacy, and Department of Pharmacy Services, University of Michigan Hospitals, Ann Arbor, Michigan.

Address correspondence to: Lynda S. Welage, PharmD, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109-1065; e-mail: lswelage{at}umich.edu.

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)-, 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-, 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.

Key Words: PEPT1 • burn • Caco-2 cells • dipeptides

This version was published on September 1, 2009

Journal of Parenteral and Enteral Nutrition, Vol. 33, No. 5, 520-528 (2009)
DOI: 10.1177/0148607109333002


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