{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:27:36Z","timestamp":1786526856119,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Oxidative and nitrosative stress contribute to epileptogenesis and seizure-related neuronal injury through iron-mediated reactive oxygen species generation and excessive nitric oxide production. This study examined whether combining valproate (VALP) with the iron chelator deferoxamine (DFO) produces additional electrophysiological or biochemical effects in a penicillin-induced model of epileptiform activity. Male Wistar rats were assigned to four groups (n = 7\/group): penicillin control, VALP (500 mg\/kg), DFO (100 mg\/kg), and VALP + DFO. Epileptiform activity was induced by intracortical penicillin and monitored by electrocorticography for 180 min, and spike frequency, spike amplitude, serum and hippocampal total antioxidant status, total oxidant status, oxidative stress index, and nitric oxide levels were measured. VALP, DFO, and their combination significantly reduced spike frequency and amplitude versus penicillin. Although VALP + DFO did not further suppress spike frequency or spike amplitude compared with VALP alone, the combination was associated with selected biochemical differences, including lower serum and hippocampal nitrite\/nitrate surrogate levels and higher hippocampal total antioxidant status. These findings suggest that VALP + DFO produces selected, marker-specific biochemical changes beyond VALP monotherapy, without providing additional anticonvulsant efficacy in this acute model. The functional significance of these biochemical changes remains to be established.<\/jats:p>","DOI":"10.3390\/biology15161375","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:57:26Z","timestamp":1786521446000},"page":"1375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Valproate and Deferoxamine on Epileptiform Activity, Oxidative Stress, and Nitric Oxide in a Penicillin-Induced Epilepsy Model"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5420-3546","authenticated-orcid":false,"given":"Arzuhan","family":"\u00c7etinda\u011f","sequence":"first","affiliation":[{"name":"Vocational School of Health Services, Sivas Cumhuriyet University, 58140 Sivas, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1783-3618","authenticated-orcid":false,"given":"\u015eeyma","family":"\u00d6zsoy","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Tokat Gaziosmanpasa University, 60100 Tokat, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4374-9025","authenticated-orcid":false,"given":"Levent","family":"Hacis\u00fcleyman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Fenerbah\u00e7e University, 34758 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0329-1974","authenticated-orcid":false,"given":"Ziya","family":"\u00c7akir","sequence":"additional","affiliation":[{"name":"Department of Oral and Dental Health, Faculty of Health Services Vocational School, Tokat Gaziosmanpasa University, 60100 Tokat, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4195-0884","authenticated-orcid":false,"given":"Elif Azize \u00d6z\u015fahin","family":"Deliba\u015f","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, Faculty of Health Sciences, Tokat Gaziosmanpasa University, 60100 Tokat, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e11073","DOI":"10.1016\/j.heliyon.2022.e11073","article-title":"Anti-seizure medications and quality of life in person with epilepsy","volume":"8","author":"Dwivedi","year":"2022","journal-title":"Heliyon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s42494-023-00137-0","article-title":"Biomolecular mechanisms of epileptic seizures and epilepsy: A review","volume":"5","author":"Sumadewi","year":"2023","journal-title":"Acta Epileptol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Aguirre, P., Mena, N., Tapia, V., Arredondo, M., and N\u00fa\u00f1ez, M.T. 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