Journal Article

Characterizing Autophagy in the Cold Ischemic Injury of Small Bowel Grafts: Evidence from Rat Jejunum

Nagy, Tibor, Caleb, Ibitamuno, Sétáló, György, Erlitz, Luca, Takács, Ildikó, Telek, Vivien, Vecsernyés, Mónika, Hardi, Péter, Jancsó, Gábor

2021

Overview

Cold ischemic injury to the intestine during preservation remains an unresolved issue in transplantation medicine. Autophagy, a cytoplasmic protein degradation pathway, is essential for metabolic adaptation to starvation, hypoxia, and ischemia. It has been implicated in the cold ischemia (CI) of other transplantable organs. This study determines the changes in intestinal autophagy evoked by cold storage and explores the effects of autophagy on ischemic grafts. Cold preservation was simulated by placing the small intestines of Wistar rats in an IGL-1 (Institute George Lopez) solution at 4 °C for varying periods (3, 6, 9, and 12 h). The extent of graft preservation injury (mucosal and cellular injury) and changes in autophagy were measured after each CI time. Subsequently, we determined the differences in apoptosis and preservation injury after activating autophagy with rapamycin or inhibiting it with 3-methyladenine. The results revealed that ischemic injury and autophagy were induced by cold storage. Autophagy peaked at 3 h and subsequently declined. After 12 h of storage, autophagic expression was reduced significantly. Additionally, enhanced intestinal autophagy by rapamycin was associated with less tissue, cellular, and apoptotic damage during and after the 12-h long preservation. After reperfusion, grafts with enhanced autophagy still presented with less injury. Inhibiting autophagy exhibited the opposite trend. These findings demonstrate intestinal autophagy changes in cold preservation. Furthermore, enhanced autophagy was protective against cold ischemia–reperfusion damage of the small bowels.

• Publisher: MDPI AG,MDPI
• Subject: Apoptosis / Autophagy / cold preservation / Cryopreservation / Hypoxia / Ischemia / ischemia–reperfusion / Jejunum / Microscopy / Mucosa / mucosal injury / Phagocytosis / Protein expression / Proteins / Rapamycin / Reperfusion / small bowel grafts / Small intestine / Transplantation