The Effects of Rapamycin on the Intestinal Graft in a Rat Model of Cold Ischemia Perfusion and Preservation

Attenuating the rheological and structural consequences of intestinal ischemia-reperfusion-injury (IRI) is important in transplant proceedings. Preconditioning is an often-proposed remedy. This technique uses physical or pharmacological methods to manipulate key ischemia pathways, such as oxidation,...

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Main Authors: Ibitamuno Caleb, Benedek Kasza, Luca Erlitz, Dávid Semjén, Péter Hardi, Lilla Makszin, Szilárd Rendeki, Ildikó Takács, Tibor Nagy, Gábor Jancsó
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/12/9/794
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author Ibitamuno Caleb
Benedek Kasza
Luca Erlitz
Dávid Semjén
Péter Hardi
Lilla Makszin
Szilárd Rendeki
Ildikó Takács
Tibor Nagy
Gábor Jancsó
author_facet Ibitamuno Caleb
Benedek Kasza
Luca Erlitz
Dávid Semjén
Péter Hardi
Lilla Makszin
Szilárd Rendeki
Ildikó Takács
Tibor Nagy
Gábor Jancsó
author_sort Ibitamuno Caleb
collection DOAJ
description Attenuating the rheological and structural consequences of intestinal ischemia-reperfusion-injury (IRI) is important in transplant proceedings. Preconditioning is an often-proposed remedy. This technique uses physical or pharmacological methods to manipulate key ischemia pathways, such as oxidation, inflammation, and autophagy, prior to ischemia. This study determined the time-dependent effects of Rapamycin preconditioning on small-bowel grafts undergoing cold ischemia perfusion and preservation. Our main parameters were mucosa and cell injury and autophagy. A total of 30 male Wistar rats were divided into 5 groups: sham, preservation-control, and 3 treated groups (Rapamycin administered either 0, 30, or 60 min prior to perfusion). After perfusion, the intestines were placed in chilled IGL-1 solution for 12 h. Thereafter, they were reperfused. Histology and bioanalysis (LDH and lactate) were used to ascertain intestinal injury while immunohistochemistry was used for measuring changes in autophagy markers (Beclin-1, LC3B, and p62 proteins). The results show no significant difference amongst the groups after vascular perfusion. However, intestinal injury findings and autophagy changes demonstrate that administering Rapamycin 30 min or 60 min prior was protective against adverse cold ischemia and reperfusion of the intestinal graft. These findings show that Rapamycin is protective against cold ischemia of the small intestine, especially when administered 30 min before the onset.
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spelling doaj.art-88d65ac093ca40f080f37b6fc94b918d2023-11-23T17:43:45ZengMDPI AGMetabolites2218-19892022-08-0112979410.3390/metabo12090794The Effects of Rapamycin on the Intestinal Graft in a Rat Model of Cold Ischemia Perfusion and PreservationIbitamuno Caleb0Benedek Kasza1Luca Erlitz2Dávid Semjén3Péter Hardi4Lilla Makszin5Szilárd Rendeki6Ildikó Takács7Tibor Nagy8Gábor Jancsó9Medical Skills Education and Innovation Centre, University of Pécs Medical School, 7624 Pécs, HungaryMedical Skills Education and Innovation Centre, University of Pécs Medical School, 7624 Pécs, HungaryMedical Skills Education and Innovation Centre, University of Pécs Medical School, 7624 Pécs, HungaryInstitute of Pathology, University of Pécs Medical School, 7624 Pécs, HungaryMedical Skills Education and Innovation Centre, University of Pécs Medical School, 7624 Pécs, HungaryInstitute of Bioanalysis, University of Pécs Medical School, 7624 Pécs, HungaryMedical Skills Education and Innovation Centre, University of Pécs Medical School, 7624 Pécs, HungaryInstitute of Nutrional Science and Dietetics, Faculty of Health Sciences, University of Pécs, 7621 Pécs, HungaryVascular Surgery Clinic, University of Pécs Medical School, 7624 Pécs, HungaryVascular Surgery Clinic, University of Pécs Medical School, 7624 Pécs, HungaryAttenuating the rheological and structural consequences of intestinal ischemia-reperfusion-injury (IRI) is important in transplant proceedings. Preconditioning is an often-proposed remedy. This technique uses physical or pharmacological methods to manipulate key ischemia pathways, such as oxidation, inflammation, and autophagy, prior to ischemia. This study determined the time-dependent effects of Rapamycin preconditioning on small-bowel grafts undergoing cold ischemia perfusion and preservation. Our main parameters were mucosa and cell injury and autophagy. A total of 30 male Wistar rats were divided into 5 groups: sham, preservation-control, and 3 treated groups (Rapamycin administered either 0, 30, or 60 min prior to perfusion). After perfusion, the intestines were placed in chilled IGL-1 solution for 12 h. Thereafter, they were reperfused. Histology and bioanalysis (LDH and lactate) were used to ascertain intestinal injury while immunohistochemistry was used for measuring changes in autophagy markers (Beclin-1, LC3B, and p62 proteins). The results show no significant difference amongst the groups after vascular perfusion. However, intestinal injury findings and autophagy changes demonstrate that administering Rapamycin 30 min or 60 min prior was protective against adverse cold ischemia and reperfusion of the intestinal graft. These findings show that Rapamycin is protective against cold ischemia of the small intestine, especially when administered 30 min before the onset.https://www.mdpi.com/2218-1989/12/9/794small bowel preservationintestinal mucosa injuryintestinal perfusioncold ischemia-reperfusionRapamycinpreconditioning
spellingShingle Ibitamuno Caleb
Benedek Kasza
Luca Erlitz
Dávid Semjén
Péter Hardi
Lilla Makszin
Szilárd Rendeki
Ildikó Takács
Tibor Nagy
Gábor Jancsó
The Effects of Rapamycin on the Intestinal Graft in a Rat Model of Cold Ischemia Perfusion and Preservation
Metabolites
small bowel preservation
intestinal mucosa injury
intestinal perfusion
cold ischemia-reperfusion
Rapamycin
preconditioning
title The Effects of Rapamycin on the Intestinal Graft in a Rat Model of Cold Ischemia Perfusion and Preservation
title_full The Effects of Rapamycin on the Intestinal Graft in a Rat Model of Cold Ischemia Perfusion and Preservation
title_fullStr The Effects of Rapamycin on the Intestinal Graft in a Rat Model of Cold Ischemia Perfusion and Preservation
title_full_unstemmed The Effects of Rapamycin on the Intestinal Graft in a Rat Model of Cold Ischemia Perfusion and Preservation
title_short The Effects of Rapamycin on the Intestinal Graft in a Rat Model of Cold Ischemia Perfusion and Preservation
title_sort effects of rapamycin on the intestinal graft in a rat model of cold ischemia perfusion and preservation
topic small bowel preservation
intestinal mucosa injury
intestinal perfusion
cold ischemia-reperfusion
Rapamycin
preconditioning
url https://www.mdpi.com/2218-1989/12/9/794
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