{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T22:49:30Z","timestamp":1767912570021,"version":"3.49.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Domp\u00e9 Farmaceutici S.p.A.","award":["DM 02\/08\/2019"],"award-info":[{"award-number":["DM 02\/08\/2019"]}]},{"name":"Domp\u00e9 Farmaceutici S.p.A.","award":["DD 02\/10\/2019"],"award-info":[{"award-number":["DD 02\/10\/2019"]}]},{"name":"Ladarixin as new Juvenile Diabetes Inhibitory Agent (LJDIA)","award":["DM 02\/08\/2019"],"award-info":[{"award-number":["DM 02\/08\/2019"]}]},{"name":"Ladarixin as new Juvenile Diabetes Inhibitory Agent (LJDIA)","award":["DD 02\/10\/2019"],"award-info":[{"award-number":["DD 02\/10\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chemokine (CXC motif) ligand 8 (CXCL8) is a pro-inflammatory chemokine binding to CXC motif receptors 1\/2 (CXCR1\/2). Patients with temporal lobe epilepsy (TLE) exhibit increased serum CXCL8 levels. CXC motif ligand 1 (CXCL1), a murine ortholog of CXCL8, has been implicated in seizure generation and neuronal loss. This study evaluated the antiepileptogenic and antiseizure effects of reparixin in amygdaloid kindling rat model of TLE. Reparixin was administered during the kindling period for 14 days, and seizures were induced twice daily via electrical stimulation. To assess the antiseizure effects, reparixin was administered to fully kindled animals, and stimulations were performed 24 and 48 h later. Levetiracetam, a broad-spectrum antiseizure drug, was administered intraperitoneally (i.p.) as positive control 1 h before each stimulation. Reparixin delayed secondary seizure generalization during kindling. Reparixin reduced seizure severity and after-discharge duration in fully kindled animals at 24 h from treatment initiation. CXCR1\/2 and protein kinase B pathway proteins exhibited no significant changes; reparixin reduced the phospho-extracellular signal-regulated kinase (pERK)\/ERK ratio in the cortex and hippocampus. CXCL1 expression was significantly decreased in the cortex. Reparixin exhibited antiepileptogenic and partial antiseizure effects by modulating the CXCL1\u2013CXCR1\/2 axis and reducing ERK signaling. Already in clinical trials on respiratory diseases, reparixin could be repurposed for epilepsy therapy.<\/jats:p>","DOI":"10.3390\/ijms26072831","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T04:58:38Z","timestamp":1742533118000},"page":"2831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reparixin as a Potential Antiepileptogenic Agent: Modulation of the CXCL1\u2013CXCR1\/2 Axis and Seizure Activity in a Kindling Rat Model of Temporal Lobe Epilepsy"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6254-4319","authenticated-orcid":false,"given":"Nihan","family":"\u00c7ar\u00e7ak","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Istanbul University, 34116 Istanbul, T\u00fcrkiye"},{"name":"Department of Neuroscience, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, 34684 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5303-8681","authenticated-orcid":false,"given":"Nursima","family":"Mutlu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, 34684 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9413-3714","authenticated-orcid":false,"given":"Elif Tu\u011f\u00e7e","family":"Erdeve","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Health Sciences, Istanbul University, 34126 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3377-2045","authenticated-orcid":false,"given":"Talat Taygun","family":"Turan","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, 34684 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6zge","family":"Sar\u0131y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, 34684 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5599-4917","authenticated-orcid":false,"given":"Canan","family":"Ulusoy","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34093 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elif","family":"\u015eanl\u0131","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34093 Istanbul, 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