{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:58:53Z","timestamp":1777021133262,"version":"3.51.4"},"reference-count":85,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Cisplatin is a potent chemotherapeutic agent whose clinical utility is limited by severe side effects, including neurotoxicity affecting the ocular system. The pathophysiology involves oxidative stress and mitochondrial dysfunction, to which the retina is particularly vulnerable. Selenium (Se), an essential trace element and component of antioxidant enzymes, has shown potential in mitigating cisplatin toxicity, although its efficacy with respect to retinal structure and the influence of administration routes remain underexplored. This study aimed to evaluate the protective efficacy of selenium against cisplatin-induced retinal toxicity and compare the effects of intraperitoneal and oral selenium administration. Methods: Forty adult male Wistar rats were randomized into four groups (n = 10 each): Group A (Cisplatin Monotherapy, 3.5 mg\/kg IP for 5 days; cumulative dose 17.5 mg\/kg); Group B (Cisplatin + Intraperitoneal Selenium, 2.73 mg\/kg; cumulative dose 60 mg\/kg); Group C (Control); and Group D (Cisplatin + Oral Selenium). Selenium prophylaxis, administered as sodium selenite (Na2SeO3), began two days prior to cisplatin administration and continued for 15 days post-treatment. Retinal evaluation two weeks after cisplatin cessation included light microscopy, semi-quantitative immunohistochemical (IHC) analysis for inflammatory (IL-6) and fibrotic (TGF-\u03b22) markers, and Transmission Electron Microscopy (TEM) for ultrastructural analysis, which were the primary endpoints. Statistical differences in the IHC scores were analyzed via the Kruskal-Wallis H test with Dunn\u2019s post hoc comparisons. Results: Cisplatin monotherapy (Group A) caused severe disruption of the retinal architecture, including edema, reactive gliosis, and significant upregulation of IL-6 and TGF-\u03b22. Ultrastructural analysis revealed mitochondrial swelling (cristolysis) and photoreceptor disk fragmentation. Intraperitoneal selenium (Group B) was associated with significant structural preservation and intact mitochondria, with TGF-\u03b22 levels comparable to those of the controls, although the IL-6 level remained moderately elevated. Conversely, oral selenium (Group D) suppressed both IL-6 and TGF-\u03b22 expression to near-negative levels but provided less ultrastructural protection, resulting in persistent mitochondrial swelling and focal photoreceptor disruption. Conclusions: Systemic cisplatin induces severe subcellular retinal toxicity characterized by mitochondrial damage and photoreceptor degeneration. Selenium supplementation attenuates these effects; however, outcome patterns differ by administration route. Intraperitoneal selenium was associated with greater morphological and ultrastructural preservation despite persistent IL-6 elevation, whereas oral selenium normalized immunohistochemical marker expression to near-control levels but was associated with more pronounced residual subcellular damage on qualitative TEM assessment. These preliminary morphological and immunohistochemical findings suggest that the route of selenium delivery may influence its neuroprotective profile; however, pharmacokinetic measurements and functional retinal assessments, such as electroretinography, are warranted before its clinical translation.<\/jats:p>","DOI":"10.3390\/nu18081236","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T15:47:02Z","timestamp":1776181622000},"page":"1236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Efficacy of Selenium in Cisplatin-Induced Retinal Toxicity: An Experimental Immunohistochemical and Ultrastructural Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1632-821X","authenticated-orcid":false,"given":"Ioannis","family":"Konstantinidis","sequence":"first","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1703-6980","authenticated-orcid":false,"given":"Sophia","family":"Tsokkou","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6336-1335","authenticated-orcid":false,"given":"Pavlos","family":"Pavlidis","sequence":"additional","affiliation":[{"name":"Department of Otorhinolarhingology, Head and Neck Surgery, University Medical Center Mainz, 55131 Mainz, Germany"},{"name":"Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6138-0970","authenticated-orcid":false,"given":"Kyriaki","family":"Papadopoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3325-2752","authenticated-orcid":false,"given":"Dimitrios","family":"Kavvadas","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5651-7082","authenticated-orcid":false,"given":"Vasilis-Spyridon","family":"Tseriotis","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Department of Neurology, Agios Pavlos General Hospital of Thessaloniki, 55134 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4900-8911","authenticated-orcid":false,"given":"Georgios","family":"Delis","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6410-2992","authenticated-orcid":false,"given":"Chrysanthi","family":"Sardeli","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3615-9745","authenticated-orcid":false,"given":"Dimitrios","family":"Kouvelas","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Siogka","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0709-5407","authenticated-orcid":false,"given":"Theodora","family":"Papamitsou","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6309-8410","authenticated-orcid":false,"given":"Sofia","family":"Karachrysafi","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","unstructured":"Edward, C., and DeVita, 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