Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model

STRINGA, PABLO; ROMANIN, DAVID; LAUSADA, NATALIA; PAPA GOBBI, RODRIGO; ZANUZZI, CAROLINA; MARTÍN, PEDRO; ABATE, JUAN CRUZ; CABANNE, ANA; ARNAL, NATHALIE; VECCHIO, LEANDRO; MILESI, VERÓNICA; PORTIANSKY, ENRIQUE; GONDOLESI, GABRIEL; RUMBO, MARTIN

Transplantation Direct

Wolters Kluwer

Año: 2017 vol. 3

2373-8731

Background. Intestinal transplantation (ITx) faces many challenges due to the complexity of surgery and to the multiple immunologicalreactions that lead to the necessity of rigorous follow-up for early detection of acute cellular rejection (ACR). Our aim wasto determine the kinetics of ACR using an experimental ITx model, with emphasis in the characterization of the process usingdifferent approaches, including the use of functional assays of absorptive and barrier function. Methods. ITx in rats conductingserial sampling was performed. Clinical monitoring, graft histology, proinflammatory gene expression, and nitrosative stress determinationwere performed. Also, glucose absorption, barrier function using ovalbumin translocation, and contractile function were analyzed.Results. The model used reproduced the different stages of ACR. Allogeneic ITx recipients showed signs of rejection frompostoperative day (POD) 5, with increasing severity until 12 POD. Histological evaluation showed mild rejection in early sampling andsevere rejection at late stages, with alterations in all graft layers. IL-6, CXCL 10, IFNg, and nitrite plasmas levels showed behaviorcoincident with histopathology. Remarkably, allogeneic grafts showed a marked alteration of glucose absorptive capacity fromPOD 5 that was sustained until endpoint. Coincidently, barrier function alteration was evidenced by luminal ovalbumin translocationto serum. Contractile function was progressively impaired along ACR. Conclusions. Glucose absorption and barrier function arealtered at early stages of ACR when histological alterations or gene expression changes were much subtle. This observation mayprovide simple evaluation tools that could be eventually translated to the clinics to contribute to early ACR diagnosis.