Metabotropic glutamate receptor blockade reduces preservation damage in livers from donors after cardiac death
Articolo
Data di Pubblicazione:
2021
Citazione:
Metabotropic glutamate receptor blockade reduces preservation damage in livers from donors after cardiac death / L.G. Di Pasqua, C. Berardo, M. Cagna, R. Verta, D. Collotta, F. Nicoletti, A. Ferrigno, M. Collino, M. Vairetti. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:5(2021), pp. 2234.1-2234.12. [10.3390/ijms22052234]
Abstract:
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 fac-tor-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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
DCD; Ischemia/reperfusion; Liver; MGluR5; MPEP; Preservation; Animals; Cold Ischemia; Liver; Liver Transplantation; Male; Organ Preservation; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate; Reperfusion Injury; Tissue Donors; Warm Ischemia; Death
Elenco autori:
L.G. Di Pasqua, C. Berardo, M. Cagna, R. Verta, D. Collotta, F. Nicoletti, A. Ferrigno, M. Collino, M. Vairetti
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