Cargando…
Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death
We previously demonstrated that the blockade of mGluR5 by 2-methyl-6(phenylethynyl)pyridine (MPEP) reduces both cold and warm ischemia/reperfusion injury. Here we evaluated whether MPEP reduces the hepatic preservation injury in rat livers from cardiac-death-donors (DCDs). Livers from DCD rats were...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956702/ https://www.ncbi.nlm.nih.gov/pubmed/33668105 http://dx.doi.org/10.3390/ijms22052234 |
_version_ | 1783664497096916992 |
---|---|
author | Di Pasqua, Laura Giuseppina Berardo, Clarissa Cagna, Marta Verta, Roberta Collotta, Debora Nicoletti, Ferdinando Ferrigno, Andrea Collino, Massimo Vairetti, Mariapia |
author_facet | Di Pasqua, Laura Giuseppina Berardo, Clarissa Cagna, Marta Verta, Roberta Collotta, Debora Nicoletti, Ferdinando Ferrigno, Andrea Collino, Massimo Vairetti, Mariapia |
author_sort | Di Pasqua, Laura Giuseppina |
collection | PubMed |
description | We previously demonstrated that the blockade of mGluR5 by 2-methyl-6(phenylethynyl)pyridine (MPEP) reduces both cold and warm ischemia/reperfusion injury. Here we evaluated whether MPEP reduces the hepatic preservation injury in rat livers from cardiac-death-donors (DCDs). Livers from DCD rats were isolated after an in situ warm ischemia (30 min) and preserved for 22 h at 4 °C with UW solution. Next, 10 mg/Kg MPEP or vehicle were administered 30 min before the portal clamping and added to the UW solution (3 µM). LDH released during washout was quantified. Liver samples were collected for iNOS, eNOS, NO, TNF-α, ICAM-1, caspase-3 and caspase-9 protein expression and nuclear factor-erythroid-2-related factor-2 (Nrf2) gene analysis. Lower LDH levels were detected in control grafts versus DCD groups. An increase in eNOS and NO content occurred after MPEP treatment; iNOS and TNF-α content was unchanged. ICAM-1 expression was reduced in the MPEP-treated livers as well as the levels of caspase-3 and caspase-9. Nrf2, oxidative stress-sensitive gene, was recovered to control value by MPEP. These results suggest that MPEP can be used to reclaim DCD livers subjected to an additional period of cold ischemia during hypothermic storage. MPEP protects against apoptosis and increased eNOS, whose overexpression has been previously demonstrated to be protective in hepatic ischemia/reperfusion damage. |
format | Online Article Text |
id | pubmed-7956702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79567022021-03-16 Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death Di Pasqua, Laura Giuseppina Berardo, Clarissa Cagna, Marta Verta, Roberta Collotta, Debora Nicoletti, Ferdinando Ferrigno, Andrea Collino, Massimo Vairetti, Mariapia Int J Mol Sci Article We previously demonstrated that the blockade of mGluR5 by 2-methyl-6(phenylethynyl)pyridine (MPEP) reduces both cold and warm ischemia/reperfusion injury. Here we evaluated whether MPEP reduces the hepatic preservation injury in rat livers from cardiac-death-donors (DCDs). Livers from DCD rats were isolated after an in situ warm ischemia (30 min) and preserved for 22 h at 4 °C with UW solution. Next, 10 mg/Kg MPEP or vehicle were administered 30 min before the portal clamping and added to the UW solution (3 µM). LDH released during washout was quantified. Liver samples were collected for iNOS, eNOS, NO, TNF-α, ICAM-1, caspase-3 and caspase-9 protein expression and nuclear factor-erythroid-2-related factor-2 (Nrf2) gene analysis. Lower LDH levels were detected in control grafts versus DCD groups. An increase in eNOS and NO content occurred after MPEP treatment; iNOS and TNF-α content was unchanged. ICAM-1 expression was reduced in the MPEP-treated livers as well as the levels of caspase-3 and caspase-9. Nrf2, oxidative stress-sensitive gene, was recovered to control value by MPEP. These results suggest that MPEP can be used to reclaim DCD livers subjected to an additional period of cold ischemia during hypothermic storage. MPEP protects against apoptosis and increased eNOS, whose overexpression has been previously demonstrated to be protective in hepatic ischemia/reperfusion damage. MDPI 2021-02-24 /pmc/articles/PMC7956702/ /pubmed/33668105 http://dx.doi.org/10.3390/ijms22052234 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Di Pasqua, Laura Giuseppina Berardo, Clarissa Cagna, Marta Verta, Roberta Collotta, Debora Nicoletti, Ferdinando Ferrigno, Andrea Collino, Massimo Vairetti, Mariapia Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death |
title | Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death |
title_full | Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death |
title_fullStr | Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death |
title_full_unstemmed | Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death |
title_short | Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death |
title_sort | metabotropic glutamate receptor blockade reduces preservation damage in livers from donors after cardiac death |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956702/ https://www.ncbi.nlm.nih.gov/pubmed/33668105 http://dx.doi.org/10.3390/ijms22052234 |
work_keys_str_mv | AT dipasqualauragiuseppina metabotropicglutamatereceptorblockadereducespreservationdamageinliversfromdonorsaftercardiacdeath AT berardoclarissa metabotropicglutamatereceptorblockadereducespreservationdamageinliversfromdonorsaftercardiacdeath AT cagnamarta metabotropicglutamatereceptorblockadereducespreservationdamageinliversfromdonorsaftercardiacdeath AT vertaroberta metabotropicglutamatereceptorblockadereducespreservationdamageinliversfromdonorsaftercardiacdeath AT collottadebora metabotropicglutamatereceptorblockadereducespreservationdamageinliversfromdonorsaftercardiacdeath AT nicolettiferdinando metabotropicglutamatereceptorblockadereducespreservationdamageinliversfromdonorsaftercardiacdeath AT ferrignoandrea metabotropicglutamatereceptorblockadereducespreservationdamageinliversfromdonorsaftercardiacdeath AT collinomassimo metabotropicglutamatereceptorblockadereducespreservationdamageinliversfromdonorsaftercardiacdeath AT vairettimariapia metabotropicglutamatereceptorblockadereducespreservationdamageinliversfromdonorsaftercardiacdeath |