Protection from Ischemic Injury in the Small Intestine using Nutraceutical Nanoparticles in a Rat Model
*Maria J. Barahona1, *Vanessa Baratta1, *Michele Finotti1,2, *Renee M. Maina1, *Giorgio Caturegli1, *Taras Lysyy1, *Francesco D'Amico1,2, David C. Mulligan1, *John P. Geibel1
1Yale, New Haven, CT; 2University of Padua, Padua, Italy
Objective: In transplant medicine, small intestine is highly susceptible to ischemia. Studies have looked at abating small bowel ischemic injury and prolonging its viability so that grafts survive transplantation and remain functional. In this study, we demonstrate how calcium nutraceutical nanoparticles (15-40nm) can protect from intestinal ischemic injury in a rat model through the activation of the calcium sensing receptor (CaSR).
Design: Proximal, middle and distal 10-cm small intestinal segments were harvested and perfused via ex-vivo intestinal perfusion. Control segments were perfused extraluminally with Ringer buffer with HEPES, pH 7.4, 300 mOSm, and intraluminally with FIT-C inulin, a marker of intestinal secretion/absorption and ischemic injury. Initial experimental group was additionally perfused with 100% N2 to induce ischemia, and subsequent experimental groups were additively perfused with increasing concentrations of calcium nanoparticles. FIT-C concentrations were compared between groups.
Setting: This study was conducted in a BSL-2 laboratory and appropriate animal facilities.
Patients: Male Sprague-Dawley rats.
Interventions: Perfusion of ischemic intestine with calcium nanoparticles.
Main Outcome Measures: Intestinal viability measured by FIT-C concentration.
Results: When we exposed the small intestine (proximal, middle and distal segments) to 100% N2, the intestine developed greater ischemic damage in comparison to small intestine perfused with normal HEPES (control segments) (p<0.0001). In the same ischemic environment, the presence of 1, 2.5 and 5 mM of calcium nanoparticles provided protection from the ischemic damage (p<0.0001).
Conclusions: Given small intestine’s sensitivity to ischemia, prolonging graft viability can contribute to enhanced success of intestinal transplants. Our findings suggest that nutraceutical nanoparticles are a promising approach to ischemic injury protection in the small bowel.