{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:50:04Z","timestamp":1760233804826,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funds from the University of Pavia and the University of Turin","award":["Ricerca Locale 2019"],"award-info":[{"award-number":["Ricerca Locale 2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u00b0C 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 \u00b5M). LDH released during washout was quantified. Liver samples were collected for iNOS, eNOS, NO, TNF-\u03b1, 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-\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms22052234","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T02:07:01Z","timestamp":1614132421000},"page":"2234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0103-1493","authenticated-orcid":false,"given":"Laura Giuseppina","family":"Di Pasqua","sequence":"first","affiliation":[{"name":"Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-5843","authenticated-orcid":false,"given":"Clarissa","family":"Berardo","sequence":"additional","affiliation":[{"name":"Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Cagna","sequence":"additional","affiliation":[{"name":"Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Verta","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-7509","authenticated-orcid":false,"given":"Debora","family":"Collotta","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinando","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy"},{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2337-2897","authenticated-orcid":false,"given":"Andrea","family":"Ferrigno","sequence":"additional","affiliation":[{"name":"Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8782-3496","authenticated-orcid":false,"given":"Massimo","family":"Collino","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2464-6127","authenticated-orcid":false,"given":"Mariapia","family":"Vairetti","sequence":"additional","affiliation":[{"name":"Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.3748\/wjg.v23.i25.4500","article-title":"Localization and role of metabotropic glutamate receptors subtype 5 in the gastrointestinal tract","volume":"23","author":"Ferrigno","year":"2017","journal-title":"World J. 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