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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...

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Autores principales: Di Pasqua, Laura Giuseppina, Berardo, Clarissa, Cagna, Marta, Verta, Roberta, Collotta, Debora, Nicoletti, Ferdinando, Ferrigno, Andrea, Collino, Massimo, Vairetti, Mariapia
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
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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.
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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
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