{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:02:28Z","timestamp":1785420148464,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marmara University Scientific Research Project Unit","award":["TDK-2023-11023"],"award-info":[{"award-number":["TDK-2023-11023"]}]},{"name":"Marmara University Scientific Research Project Unit","award":["TDK-2025-11380"],"award-info":[{"award-number":["TDK-2025-11380"]}]},{"award":["TDK-2023-11023"],"award-info":[{"award-number":["TDK-2023-11023"]}],"id":[{"id":"https:\/\/ror.org\/02kswqa67","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TDK-2025-11380"],"award-info":[{"award-number":["TDK-2025-11380"]}],"id":[{"id":"https:\/\/ror.org\/02kswqa67","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Scientific and Technological Research Council of Turkey Health Institutes","award":["38924"],"award-info":[{"award-number":["38924"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epilepsy is associated with impaired reproductive function and testicular pathologies. Intermittent fasting (IF) is a nonpharmacological metabolic intervention with anti-inflammatory and antioxidant effects. This study investigated the protective effects of IF on testicular damage in a genetic absence epilepsy rat model (GAERS), focusing on histomorphology, oxidative stress parameters, and hormonal profiles. Testicular tissues from Wistar control (WC), Wistar + IF (WIF), GAERS control (GC), and GAERS + IF (GIF) groups (total n = 20; 5 rats per group) were evaluated using hematoxylin and eosin and Periodic Acid\u2013Schiff staining. Apoptosis and spermatogenic cell integrity were assessed using caspase-3, P-element-induced wimpy testis (PIWI), and Deleted in Azoospermia-Like (DAZL) immunohistochemistry. Johnsen\u2019s score, seminiferous tubule diameter, and epithelial thickness were quantified. Oxidative stress markers, including catalase, malondialdehyde, glutathione, myeloperoxidase, and superoxide dismutase, were measured using spectrophotometric methods, and serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were determined using ELISA kits. The GC group showed significantly reduced Johnsen scores, tubular diameters, and epithelial thickness, along with disrupted basement membrane integrity and increased caspase-3 immunoreactivity. IF significantly improved histological parameters, restored basement membrane integrity, reduced apoptosis, and increased PIWI and DAZL expression in the GIF group. IF also ameliorated oxidative stress and elevated reproductive hormone levels, indicating positive modulation of the hypothalamic\u2013pituitary\u2013gonadal axis. In conclusion, IF reduces oxidative stress and preserves seminiferous tubules and hormonal function in genetic absence epilepsy, highlighting its potential as a supportive nonpharmacological approach to protect male reproductive health.<\/jats:p>","DOI":"10.3390\/ijms27083619","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:24:23Z","timestamp":1776673463000},"page":"3619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intermittent Fasting Ameliorates Testicular Damage via Oxidative Stress Modulation in a Genetic Absence Epilepsy Rat Model"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0674-090X","authenticated-orcid":false,"given":"Damla","family":"G\u00f6k\u00e7eo\u011flu Kayal\u0131","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, School of Medicine, Istanbul Atlas University, 34408 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatice","family":"Mara\u015f","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, School of Medicine, Marmara University, 34854 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayb\u00fcke","family":"\u00c7ilingir","sequence":"additional","affiliation":[{"name":"School of Medicine, Marmara University, 34854 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5859-3972","authenticated-orcid":false,"given":"Ahmet An\u0131l","family":"Keskin","sequence":"additional","affiliation":[{"name":"School of Medicine, Marmara University, 34854 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9712-0448","authenticated-orcid":false,"given":"\u00c7a\u011fan","family":"Yard\u0131mc\u0131","sequence":"additional","affiliation":[{"name":"School of Medicine, Marmara University, 34854 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Beyza","family":"Aykurt","sequence":"additional","affiliation":[{"name":"School of Medicine, Marmara University, 34854 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7376-9403","authenticated-orcid":false,"given":"Eda Nur","family":"Arslan","sequence":"additional","affiliation":[{"name":"School of Medicine, Marmara University, 34854 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7933-4262","authenticated-orcid":false,"given":"Bircan","family":"Kolba\u015f\u0131-Erkan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, School of Medicine, Istanbul Medipol University, 34815 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9485-0174","authenticated-orcid":false,"given":"Zarife Nigar","family":"\u00d6zdemir-Kumral","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Marmara University, 34854 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2591-9174","authenticated-orcid":false,"given":"Ozlem Tugce","family":"Cilingir-Kaya","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, School of Medicine, Marmara University, 34854 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48573","DOI":"10.1007\/s11356-022-19251-6","article-title":"Anti-kindling effect of Ginkgo biloba leaf extract and L-carnitine in the pentylenetetrazol model of epilepsy","volume":"29","author":"Essawy","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.brainresbull.2020.08.009","article-title":"Salidroside shows anticonvulsant and neuroprotective effects in a pentylenetetrazol-kindling epileptic model","volume":"164","author":"Wu","year":"2020","journal-title":"Brain Res. Bull."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/S0140-6736(06)68477-8","article-title":"Adult epilepsy","volume":"367","author":"Duncan","year":"2006","journal-title":"Lancet"},{"key":"ref_4","first-page":"34","article-title":"Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications","volume":"15","author":"Umesh","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1097\/chi.0b013e31815597fc","article-title":"Psychiatric problems in children with epilepsy: 10-year research update review","volume":"46","author":"Plioplys","year":"2007","journal-title":"J. Am. Acad. Child. Adolesc. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45691","DOI":"10.1038\/s41598-025-26746-y","article-title":"In vivo, in silico effects of sakuranetin as a multi-target nutraceutical against PTZ-induced seizures via GABA restoration and BDNF\/TrkB activation","volume":"15","author":"Syed","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101749","DOI":"10.1016\/j.jchemneu.2020.101749","article-title":"LncRNA CASC2 inhibits astrocytic activation and adenosine metabolism in a pentylenetetrazol-induced epilepsy model","volume":"105","author":"Zhu","year":"2020","journal-title":"J. Chem. Neuroanat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"107563","DOI":"10.1016\/j.yebeh.2020.107563","article-title":"Reproductive health in patients with epilepsy","volume":"113","author":"Markoula","year":"2020","journal-title":"Epilepsy Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106495","DOI":"10.1016\/j.yebeh.2019.106495","article-title":"Sexual dysfunction in people with epilepsy","volume":"100","author":"Rathore","year":"2019","journal-title":"Epilepsy Behav."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1056\/NEJMra1905136","article-title":"Effects of intermittent fasting on health, aging, and disease","volume":"381","author":"Mattson","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_11","first-page":"5562120","article-title":"Exploring the impact of ketogenic diet and intermittent fasting on male rats\u2019 testicular health","volume":"2023","author":"Kurt","year":"2023","journal-title":"J. Food Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.3945\/ajcn.2009.28380","article-title":"Short-term modified alternate-day fasting: A novel dietary strategy for weight loss and cardioprotection in obese adults","volume":"90","author":"Varady","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_13","first-page":"166","article-title":"The effect of fasting on testicular tissue and spermatogenesis in rats","volume":"40","author":"Razi","year":"2008","journal-title":"Andrologia"},{"key":"ref_14","first-page":"24","article-title":"Impact of caloric restriction on male reproductive function in rodents","volume":"15","author":"Sengupta","year":"2017","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.pop.2024.04.003","article-title":"Male reproductive endocrine disorders","volume":"51","author":"McCoskey","year":"2024","journal-title":"Prim. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.seizure.2007.11.007","article-title":"Disorders of reproduction in patients with epilepsy: Antiepileptic drug-related mechanisms","volume":"17","author":"Isojarvi","year":"2008","journal-title":"Seizure"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1212\/WNL.0000000000003509","article-title":"Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies","volume":"88","author":"Fiest","year":"2017","journal-title":"Neurology"},{"key":"ref_18","first-page":"212","article-title":"Women and epilepsy","volume":"14","author":"Connor","year":"2009","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1212\/01.WNL.0000098936.46730.64","article-title":"Effect of epilepsy and antiepileptic drugs on male reproductive endocrine function","volume":"62","author":"Juntunen","year":"2004","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.seizure.2007.11.025","article-title":"Disorders of reproduction in patients with epilepsy: Primary neurological mechanisms","volume":"17","author":"Herzog","year":"2008","journal-title":"Seizure"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1111\/j.0013-9580.2004.60703.x","article-title":"Differential effects of antiepileptic drugs on sexual function and reproductive hormones in men with epilepsy","volume":"45","author":"Herzog","year":"2004","journal-title":"Epilepsia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"881","DOI":"10.22271\/veterinary.2024.v9.i2l.1302","article-title":"Effect of different concentrations of hydrogen peroxide on indigenous bull sperm motility","volume":"9","author":"Thakor","year":"2024","journal-title":"Int. J. Vet. Sci. Anim. Husb."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/S0015-0282(00)01591-0","article-title":"Effect of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa","volume":"74","author":"Duru","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e14130","DOI":"10.1111\/and.14130","article-title":"Histological analysis of the effects of thymoquinone on testicular damage in pentylenetetrazole-induced temporal lobe epilepsy model","volume":"53","author":"Karakaya","year":"2021","journal-title":"Andrologia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jneumeth.2015.05.022","article-title":"The genetic absence epilepsy rat from Strasbourg as a model to decipher the neuronal and network mechanisms of generalized idiopathic epilepsies","volume":"260","author":"Depaulis","year":"2016","journal-title":"J. Neurosci. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.4067\/S0717-95022021000601709","article-title":"Immunoreactivity in the Testis Tissue of Wistar and Genetic Absence Epilepsy Rats","volume":"39","author":"Kaya","year":"2021","journal-title":"Int. J. Morphol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00394-004-0520-0","article-title":"Effects of age and dietary restriction on oxidative DNA damage, antioxidant protection and DNA repair in rats","volume":"44","author":"Gedik","year":"2005","journal-title":"Eur. J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cell.2015.02.020","article-title":"Promoting health and longevity through diet: From model organisms to humans","volume":"161","author":"Fontana","year":"2015","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cienfuegos, S., Corapi, S., Gabel, K., Ezpeleta, M., Kalam, F., Lin, S., Pavlou, V., and Varady, K.A. (2022). Effect of intermittent fasting on reproductive hormone levels in females and males: A review of human trials. Nutrients, 14.","DOI":"10.3390\/nu14112343"},{"key":"ref_30","first-page":"795259","article-title":"Oxidative stress and epilepsy: Literature review","volume":"2012","author":"Torres","year":"2012","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Albrahim, T., Alangry, R., Alotaibi, R., Almandil, L., and Alburikan, S. (2023). Effects of regular exercise and intermittent fasting on neurotransmitters, inflammation, oxidative stress, and brain-derived neurotrophic factor in cortex of ovariectomized rats. Nutrients, 15.","DOI":"10.3390\/nu15194270"},{"key":"ref_32","first-page":"828","article-title":"PIWI proteins and piRNAs in the nervous system","volume":"42","author":"Kim","year":"2019","journal-title":"Mol. Cells"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/jmcb\/mjp026","article-title":"Dazl promotes germ cell differentiation from embryonic stem cells","volume":"1","author":"Yu","year":"2009","journal-title":"J. Mol. Cell Biol."},{"key":"ref_34","first-page":"6763","article-title":"Intermittent fasting decreases oxidative stress parameters and increases total antioxidant capacity","volume":"12","author":"Sharsher","year":"2022","journal-title":"Biointerface Res. Appl. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s13668-021-00353-5","article-title":"Effect of various types of intermittent fasting on weight loss and improvement of diabetic parameters in humans","volume":"10","author":"Nowosad","year":"2021","journal-title":"Curr. Nutr. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Oduwole, O.O., Huhtaniemi, I.T., and Misrahi, M. (2021). The roles of luteinizing hormone, follicle-stimulating hormone and testosterone in spermatogenesis and folliculogenesis revisited. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312735"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12974-023-02789-8","article-title":"Inflammatory panel cytokines are elevated in the neocortex of late-stage Alzheimer\u2019s disease but not Lewy body dementias","volume":"20","author":"Chai","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_39","first-page":"IE01","article-title":"The impact of oxidative stress on testicular function and the role of antioxidants in improving it: A review","volume":"11","author":"Asadi","year":"2017","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.seizure.2007.11.015","article-title":"Seizure control and pharmacokinetics of antiepileptic drugs in pregnant women with epilepsy","volume":"17","author":"Brodtkorb","year":"2008","journal-title":"Seizure"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.freeradbiomed.2022.12.084","article-title":"Intermittent fasting reverses the declining quality of aged oocytes","volume":"195","author":"Li","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"521","DOI":"10.17221\/38\/2021-VETMED","article-title":"Morphological and morphometric adaptations of testes in broilers induced by glucocorticoid","volume":"66","author":"Islam","year":"2021","journal-title":"Vet. Med."},{"key":"ref_43","first-page":"621","article-title":"Resveratrol treatment reduces apoptosis and morphological alterations in cisplatin-induced testis damage","volume":"23","author":"Ercan","year":"2019","journal-title":"J. Res. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/aja.2011.57","article-title":"Testicular biopsy: Clinical practice and interpretation","volume":"14","author":"Dohle","year":"2011","journal-title":"Asian J. Androl."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8985","DOI":"10.1038\/s41598-020-65887-0","article-title":"Reproductive effects of subchronic exposure to acetamiprid in male rats","volume":"10","author":"Boran","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1111\/j.1528-1167.2005.00298.x","article-title":"Brain inflammation in epilepsy: Experimental and clinical evidence","volume":"46","author":"Vezzani","year":"2005","journal-title":"Epilepsia"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wilhelmi de Toledo, F., Grundler, F., Goutzourelas, N., Tekos, F., Vassi, E., Mesnage, R., and Kouretas, D. (2020). Influence of long-term fasting on blood redox status in humans. Antioxidants, 9.","DOI":"10.3390\/antiox9060496"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6337","DOI":"10.1038\/s41598-017-06870-0","article-title":"A brief exposure to cadmium impairs Leydig cell regeneration in the adult rat testis","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:30:25Z","timestamp":1776673825000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,18]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083619"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083619","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,18]]}}}