{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T19:09:35Z","timestamp":1763665775605,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005322","name":"Recep Tayyip Erdo\u011fan University Development Foundation","doi-asserted-by":"publisher","award":["02025007023652"],"award-info":[{"award-number":["02025007023652"]}],"id":[{"id":"10.13039\/501100005322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Objective: This study aimed to investigate the potential splenic tissue damage induced by radiotherapy (RT) and the potential protective effect of different doses of dexmedetomidine on this damage at the histopathological, immunohistochemical, and biochemical levels. Materials and Methods: In our study, Sprague Dawley rats were randomly divided into four groups: Control, Radiotherapy (RT; 8 Gy), RT + Dexmedetomidine 100 \u00b5g\/kg (RT-D100), and RT + Dexmedetomidine 200 \u00b5g\/kg (RT-D200). A single dose of 8 Gy radiotherapy was administered to each RT group. Spleen tissues were examined histologically with hematoxylin-eosin and immunohistochemically with anti-Caspase-3, anti-TGF-\u03b21, and anti-TGF-\u03b23 using light microscopy. TBARS and total thiol levels were also analyzed to assess oxidative stress and antioxidant capacity. Results: Histopathological results showed a significant decrease in white pulp diameter, decreased cellular density, and increased congestion in the red pulp in the RT group. Significant fibrosis, sinusoidal dilatation, vacuolization, and amyloid deposition were detected in the white pulp in the RT group. Regarding anti-caspase-3 immunoreactivity, strong positivity increased in the red pulp in the RT group, while a significant increase was observed in the white pulp in both the RT-D100 and RT groups. While the proportion of TGF-\u03b21 immunopositive cells did not change significantly in the RT group, they increased significantly in both dexmedetomidine groups (especially RT-D200). TGF-\u03b23 expression increased significantly only in the RT-D100 group. In biochemical analyses, TBARS levels increased significantly in the RT-D100 group. Total thiol levels decreased in the RT group and increased in the dexmedetomidine-treated groups. Conclusions: While RT caused histopathological damage and increased oxidative stress in spleen tissue, dexmedetomidine reduced this damage in a dose-dependent manner. The different immunohistochemical profiles of TGF-\u03b21 and TGF-\u03b23 suggest that these cytokines may have different functions in the spleen. 100 \u00b5g\/kg dexmedetomidine stimulates a regenerative response through TGF-\u03b23, while 200 \u00b5g\/kg dexmedetomidine may provide immune regulation and antioxidative defense through TGF-\u03b21.<\/jats:p>","DOI":"10.3390\/life15091430","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T07:52:28Z","timestamp":1757663548000},"page":"1430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Dose-Dependent Study Examining Dexmedetomidine\u2019s Possible Effects Against Oxidative, Fibrotic, and Apoptotic Damage Induced by Radiation Exposure in Spleen Tissue"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6815-6456","authenticated-orcid":false,"given":"Hatice","family":"Beyazal Polat","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 55139, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8324-1891","authenticated-orcid":false,"given":"Hamit","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Kahramanmara\u015f S\u00fct\u00e7\u00fc \u0130mam University, Rize 46050, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3649-8336","authenticated-orcid":false,"given":"Kagan","family":"Kilinc","sequence":"additional","affiliation":[{"name":"Department of Genetic and Bioengineering, Faculty of Engineering and Natural Sciences, Gumushane University, Gumushane 29000, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1354-0412","authenticated-orcid":false,"given":"Belemir","family":"G\u00fclhan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Samsun University, Samsun 55000, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5543-9761","authenticated-orcid":false,"given":"Sema","family":"Y\u0131lmaz Rak\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Radiation Oncology, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5387-4666","authenticated-orcid":false,"given":"Levent","family":"T\u00fcmkaya","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Ondokuz May\u0131s University, Samsun 55139, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nrc1735","article-title":"Radiation and the microenvironment\u2013tumorigenesis and therapy","volume":"5","author":"Park","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2011.12.012","article-title":"Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury","volume":"327","author":"Azzam","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1097\/HP.0000000000001601","article-title":"Radiation-induced cell death and its mechanisms","volume":"123","author":"Jiao","year":"2022","journal-title":"Health Phys."},{"key":"ref_4","first-page":"247","article-title":"Targeted and non-targeted effects of ionizing radiation","volume":"8","author":"Desouky","year":"2015","journal-title":"J. Radiat. Res. Appl. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1023\/B:CBTO.0000013342.17370.16","article-title":"Prophylactic action of melatonin against cyclophosphamide-induced oxidative stress in mice","volume":"19","author":"Manda","year":"2003","journal-title":"Cell Biol. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hong, Y., Boiti, A., Vallone, D., and Foulkes, N.S. (2024). Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution. Antioxidants, 13.","DOI":"10.3390\/antiox13030312"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.ecoenv.2006.03.008","article-title":"Ameliorative effect of melatonin against gamma-irradiation-induced oxidative stress and tissue injury","volume":"66","author":"Fayed","year":"2007","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejca.2020.10.025","article-title":"The spleen as an organ at risk in paediatric radiotherapy: A SIOP-Europe Radiation Oncology Working Group report","volume":"143","author":"Arunagiri","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1667\/RADE-20-00267.1","article-title":"Transcriptomic response in the spleen after whole-body low-dose X-ray irradiation","volume":"196","author":"Puukila","year":"2021","journal-title":"Radiat. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rittase, W.B., Slaven, J.E., Suzuki, Y.J., Muir, J.M., Lee, S.H., Rusnak, M., Brehm, G.V., Bradfield, D.T., Symes, A.J., and Day, R.M. (2022). Iron deposition and ferroptosis in the spleen in a murine model of acute radiation syndrome. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911029"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20170278","DOI":"10.1259\/bjr.20170278","article-title":"Radiation induced bystander effects in the spleen of cranially-irradiated rats","volume":"90","author":"Abdelrazzak","year":"2017","journal-title":"Br. J. Radiol."},{"key":"ref_12","first-page":"301","article-title":"Late changes in peripheral blood and spleen in mice after the effect of single whole body irradiation with the dose of 8 Gy","volume":"117","author":"Mackova","year":"1990","journal-title":"Folia Haematol. Int. Mag. Klin. Morphol. Blutforsch."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"44","DOI":"10.4255\/mcpharmacol.09.06","article-title":"Role of radiation-induced TGF-beta signaling in cancer therapy","volume":"1","author":"Dancea","year":"2009","journal-title":"Mol. Cell. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hanson, I., Pitman, K.E., and Edin, N.F.J. (2023). The role of TGF-\u03b23 in radiation response. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087614"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, X.L., Yun, J.S., Han, D., Yook, J.I., Kim, H.S., and Cho, E.S. (2020). TGF-\u03b2 Pathway in Salivary Gland Fibrosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239138"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-immunol-032713-120257","article-title":"TGF-\u03b2 activation and function in immunity","volume":"32","author":"Travis","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.it.2010.04.002","article-title":"TGF-\u03b2 and immune cells: An important regulatory axis in the tumor microenvironment and progression","volume":"31","author":"Yang","year":"2010","journal-title":"Trends Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","article-title":"Emerging roles of caspase-3 in apoptosis","volume":"6","author":"Porter","year":"1999","journal-title":"Cell Death Differ."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109337","DOI":"10.1016\/j.cellsig.2019.06.002","article-title":"Radiation induces apoptosis primarily through the intrinsic pathway in mammalian cells","volume":"62","author":"Cao","year":"2019","journal-title":"Cell Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6136105","DOI":"10.1155\/2020\/6136105","article-title":"Organ-Protective Effects and the underlying mechanism of dexmedetomidine","volume":"2020","author":"Bao","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1007\/s12640-021-00379-1","article-title":"Can Dexmedetomidine Be Effective in the Protection of Radiotherapy-Induced Brain Damage in the Rat?","volume":"39","author":"Cinar","year":"2021","journal-title":"Neurotox. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1517\/14740338.2010.512609","article-title":"Dexmedetomidine: Pediatric pharmacology, clinical uses and safety","volume":"10","author":"Su","year":"2011","journal-title":"Expert. Opin. Drug Saf."},{"key":"ref_23","first-page":"8030","article-title":"The role of dexmedetomidine in immune tissue and inflammatory diseases: A narrative review","volume":"26","author":"Chen","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0003-9861(59)90090-6","article-title":"Tissue sulfhydryl groups","volume":"82","author":"Ellman","year":"1959","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yilmaz, H., Mercantepe, F., Tumkaya, L., Mercantepe, T., Yilmaz, A., and Yilmaz Rakici, S. (2023). The potential antioxidant effect of N-acetylcysteine on X-ray ionizing radiation-induced pancreas islet cell toxicity. Biochem. Biophys. Res. Commun., 685.","DOI":"10.1016\/j.bbrc.2023.149154"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"451","DOI":"10.4103\/jomfp.jomfp_301_21","article-title":"Immunohistochemical expression of survivin in oral epithelial dysplasia and different grades of oral squamous cell carcinoma","volume":"26","author":"Ghritlahare","year":"2022","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"193","DOI":"10.7150\/ijms.3635","article-title":"Cancer and radiation therapy: Current advances and future directions","volume":"9","author":"Baskar","year":"2012","journal-title":"Int. J. Med. Sci."},{"key":"ref_29","first-page":"381","article-title":"Managing the adverse effects of radiation therapy","volume":"82","author":"Berkey","year":"2010","journal-title":"Am. Fam. Physician"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"153402","DOI":"10.1016\/j.phymed.2020.153402","article-title":"Protection against chemotherapy- and radiotherapy-induced side effects: A review based on the mechanisms and therapeutic opportunities of phytochemicals","volume":"80","author":"Liu","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jclinane.2016.06.031","article-title":"Dexmedetomidine acts as an oxidative damage prophylactic in rats exposed to ionizing radiation","volume":"34","author":"Kutanis","year":"2016","journal-title":"J. Clin. Anesth."},{"key":"ref_32","first-page":"864","article-title":"Selenium protects keratinocytes from ultraviolet radiation-induced lipid peroxidation and cell death by oxidative stress","volume":"148","author":"McKenzie","year":"2003","journal-title":"Brit. J. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.clinbiochem.2014.09.026","article-title":"A novel and automated assay for thiol\/disulphide homeostasis","volume":"47","author":"Erel","year":"2014","journal-title":"Clin. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nri1669","article-title":"Structure and function of the spleen","volume":"5","author":"Mebius","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0171-2985(80)80064-7","article-title":"Morphology of the Spleen White Pulp in Relation to the Immunological Functions in Patients with Far Advanced Bronchial-Carcinoma","volume":"157","author":"Syrjanen","year":"1980","journal-title":"Immunobiology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lee, C.F., Cheng, C.H., Hung, H.C., Lee, J.C., Wang, Y.C., Wu, T.H., Wu, T.J., Chou, H.S., Chan, K.M., and Lee, W.C. (2021). Sedative and Immunosuppressive Effects of Dexmedetomidine in Transplantation. Pharmaceuticals, 14.","DOI":"10.3390\/ph14080825"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.vetimm.2004.02.001","article-title":"Apoptosis in normal lymphoid organs from healthy normal, conventional pigs at different ages detected by TUNEL and cleaved caspase-3 immunohistochemistry in paraffin-embedded tissues","volume":"99","author":"Resendes","year":"2004","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s004290050254","article-title":"The apoptosis cascade--morphological and immunohistochemical methods for its visualization","volume":"200","author":"Huppertz","year":"1999","journal-title":"Anat. Embryol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Paganetti, H. (2023). A review on lymphocyte radiosensitivity and its impact on radiotherapy. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1201500"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/01926230600867743","article-title":"Normal structure, function, and histology of the spleen","volume":"34","author":"Cesta","year":"2006","journal-title":"Toxicol. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"16","DOI":"10.15586\/aei.v50i2.505","article-title":"Dexmedetomidine represses TGF-\u03b21-induced extracellular matrix production and proliferation of airway smooth muscle cells by inhibiting MAPK signaling pathway","volume":"50","author":"Zhou","year":"2022","journal-title":"Allergol. Immunopathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/PRS.0b013e318217429b","article-title":"Avotermin for scar improvement following scar revision surgery: A randomized, double-blind, within-patient, placebo-controlled, phase II clinical trial","volume":"128","author":"So","year":"2011","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"26134","DOI":"10.1016\/S0021-9258(18)35727-2","article-title":"Tumor necrosis factor-alpha down-regulates human elastin gene expression. Evidence for the role of AP-1 in the suppression of promoter activity","volume":"267","author":"Kahari","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1172\/JCI114866","article-title":"Tumor necrosis factor-alpha and interferon-gamma suppress the activation of human type I collagen gene expression by transforming growth factor-beta 1. Evidence for two distinct mechanisms of inhibition at the transcriptional and posttranscriptional levels","volume":"86","author":"Kahari","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"30226","DOI":"10.1074\/jbc.M005310200","article-title":"Tumor necrosis factor-\u03b1 inhibits transforming growth factor-\u03b2 \/Smad signaling in human dermal fibroblasts via AP-1 activation","volume":"275","author":"Verrecchia","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.autneu.2015.03.001","article-title":"Dexmedetomidine and regulation of splenic sympathetic nerve discharge in aged F344 rats","volume":"190","author":"McMurphy","year":"2015","journal-title":"Auton. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5076","DOI":"10.21037\/tcr-21-1765","article-title":"Association between unintentional splenic radiation and lymphopenia and high neutrophil\/lymphocyte ratio after radiotherapy in patients with esophageal cancer","volume":"10","author":"Sakaguchi","year":"2021","journal-title":"Transl. Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s13014-022-02171-7","article-title":"Radiotherapy modulates tumor cell fate decisions: A review","volume":"17","author":"Chen","year":"2022","journal-title":"Radiat. Oncol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/9\/1430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:44:16Z","timestamp":1760035456000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/9\/1430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":48,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["life15091430"],"URL":"https:\/\/doi.org\/10.3390\/life15091430","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2025,9,12]]}}}