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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MDPI AG
2022-08-01
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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. |
first_indexed | 2024-03-09T23:11:52Z |
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issn | 2218-1989 |
language | English |
last_indexed | 2024-03-09T23:11:52Z |
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series | Metabolites |
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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