{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:38:37Z","timestamp":1790386717238,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Vortioxetine is a multimodal antidepressant that modulates serotonergic, noradrenergic, and dopaminergic systems, yet its effects on female reproductive physiology remain incompletely defined. This study investigated how short- and long-term vortioxetine exposure influences reproductive function in female rats, integrating measurements of oxidative-stress biomarkers, catecholamines, and endocrine endpoints (prolactin and corticosterone). Methods: Forty-two female Wistar albino rats were randomized into seven groups (n = 6): healthy control; short-term vortioxetine; long-term vortioxetine; and the same two regimens each combined with metyrosine or metyrapone. Metyrosine and metyrapone (50 mg\/kg, oral gavage) were given 1 h before vortioxetine (10 mg\/kg). Treatments lasted one week (short-term) or four weeks (long-term). Serum MDA, tGSH, SOD, CAT, adrenaline, noradrenaline, dopamine, serotonin, prolactin, and corticosterone were measured. Fertility outcomes were assessed by co-housing females with males for one month. Results: Vortioxetine increased MDA, catecholamines, and serotonin and decreased antioxidant markers and prolactin versus controls (p &lt; 0.001). Long-term vortioxetine produced a marked rise in corticosterone that coincided with infertility and delayed parturition. Metyrosine lowered oxidative stress and catecholamines but did not reverse infertility. In contrast, metyrapone blunted corticosterone elevation and preserved reproductive capacity. Conclusions: Long-term vortioxetine induced infertility in female rats, likely mediated by corticosterone elevation consistent with hypothalamic\u2013pituitary\u2013adrenal axis dysregulation. These findings suggest the need to monitor reproductive risk when considering vortioxetine in women of reproductive age and warrant further mechanistic and translational studies.<\/jats:p>","DOI":"10.3390\/ph18111690","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T14:55:15Z","timestamp":1762527315000},"page":"1690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Short- and Long-Term Vortioxetine Administration on Reproductive Function in Female Rats"],"prefix":"10.3390","volume":"18","author":[{"given":"Eda","family":"Bingul","sequence":"first","affiliation":[{"name":"Gynecology and Obstetrics Clinic, Erzurum City Hospital, 25240 Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Hizal","sequence":"additional","affiliation":[{"name":"Gynecology and Obstetrics Clinic, Private Medicabil Hospital, 16350 Bursa, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozgecan","family":"Keles","sequence":"additional","affiliation":[{"name":"Gynecology and Obstetrics Clinic, Erzurum City Hospital, 25240 Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5431-111X","authenticated-orcid":false,"given":"Nurinisa","family":"Yucel","sequence":"additional","affiliation":[{"name":"Pharmacy Services Program, Vocational School of Health Services, Erzincan Binali Yildirim University, 24100 Erzincan, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"Suleyman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Nursing, Faculty of Health Sciences, Erzincan Binali Yildirim University, 24030 Erzincan, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Gunay","sequence":"additional","affiliation":[{"name":"Medical Biochemistry Clinic, Mengucek Gazi Education and Research Hospital, 24100 Erzincan, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Yasar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Erzincan Binali Y\u0131ld\u0131r\u0131m University, 24030 Erzincan, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-4099","authenticated-orcid":false,"given":"Halis","family":"Suleyman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, 24030 Erzincan, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s40262-017-0612-7","article-title":"Vortioxetine: Clinical pharmacokinetics and drug interactions","volume":"57","author":"Chen","year":"2018","journal-title":"Clin. Pharmacokinet."},{"key":"ref_2","unstructured":"(2025, October 29). Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK548752\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1021\/jm101459g","article-title":"Discovery of 1-[2-(2, 4-dimethylphenylsulfanyl) phenyl] piperazine (Lu AA21004): A novel multimodal compound for the treatment of major depressive disorder","volume":"54","author":"Ruhland","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.12740\/PP\/OnlineFirst\/151570","article-title":"Vortioxetine-pharmacological properties and use in mood disorders. The current state of knowledge","volume":"57","author":"Krupa","year":"2023","journal-title":"Psychiatr. Pol."},{"key":"ref_5","first-page":"81","article-title":"Antidepressz\u00edvumok, stresszorok \u00e9s a szerotonin 1A receptor","volume":"17","author":"Kirilly","year":"2015","journal-title":"Neuropsychopharmacol. Hung."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.phrs.2019.02.006","article-title":"Chronic vortioxetine treatment improves the responsiveness to an acute stress acting through the ventral hippocampus in a glucocorticoid-dependent way","volume":"142","author":"Brivio","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3109\/01485018908986755","article-title":"Blood serotonin levels and male infertility","volume":"22","author":"Gonzales","year":"1989","journal-title":"Arch. Androl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1530\/acta.0.1040266","article-title":"Mechanism of serotonin effects on prolactin and growth hormone secretion in domestic fowl","volume":"104","author":"Hall","year":"1983","journal-title":"Eur. J. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/0306-4522(92)90047-6","article-title":"Serotonin-induced stimulation of cortisol secretion from human adrenocortical tissue is mediated through activation of a serotonin4 receptor subtype","volume":"47","author":"Lefebvre","year":"1992","journal-title":"Neuroscience"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wdowiak, A., Raczkiewicz, D., Janczyk, P., Bojar, I., Makara-Studzi\u0144ska, M., and Wdowiak-Filip, A. (2020). Interactions of cortisol and prolactin with other selected menstrual cycle hormones affecting the chances of conception in infertile women. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17207537"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1093\/humrep\/des383","article-title":"The risks of selective serotonin reuptake inhibitor use in infertile women: A review of the impact on fertility, pregnancy, neonatal health and beyond","volume":"28","author":"Domar","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Anwar, M.M., and Laila, I.M.I. (2024). The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-024-04447-9"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Caruso, G., Grasso, M., Fidilio, A., Torrisi, S.A., Musso, N., Geraci, F., Tropea, M.R., Privitera, A., Tascedda, F., and Puzzo, D. (2021). Antioxidant activity of fluoxetine and vortioxetine in a non-transgenic animal model of alzheimer\u2019s disease. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.809541"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.31557\/APJCP.2023.24.3.1007","article-title":"Protective effect of adenosine triphosphate against 5-Fluorouracil-Induced oxidative ovarian damage in vivo","volume":"24","author":"Ozer","year":"2023","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Demirci-\u00c7eki\u00e7, S., \u00d6zkan, G., Avan, A.N., Uzunboy, S., \u00c7apano\u011flu, E., and Apak, R. (2022). Biomarkers of oxidative stress and antioxidant defense. J. Pharm. Biomed. Anal., 209.","DOI":"10.1016\/j.jpba.2021.114477"},{"key":"ref_16","first-page":"453","article-title":"Alterations in hippocampal antioxidant enzyme activities and sympatho-adrenomedullary system of rats in response to different stress models","volume":"55","author":"Dronjak","year":"2006","journal-title":"Physiol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101","DOI":"10.51248\/.v44i1.2145","article-title":"Relation of catecholamines with oxidative stress in patients undergoing cardiac surgery before and after endotracheal intubation","volume":"44","author":"Sah","year":"2024","journal-title":"Biomedicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"331","DOI":"10.33549\/physiolres.932449","article-title":"Pheochromocytoma and markers of oxidative stress","volume":"62","author":"Turkova","year":"2013","journal-title":"Physiol. Res"},{"key":"ref_19","unstructured":"Brunton, L.L., Knollmann, B.C., and Hilal-Dandan, R. (2018). Goodman & Gilman\u2019s the Pharmacological Basis of Therapeutics, McGraw-Hill Education."},{"key":"ref_20","first-page":"e230006","article-title":"Metyrosine-associated endocrinological changes in pheochromocytoma and paraganglioma","volume":"3","author":"Matsuo","year":"2023","journal-title":"Endocr. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e20201586","DOI":"10.1590\/0001-3765202320201586","article-title":"The effects of metyrosine on ischemia-reperfusion-induced oxidative ovarian injury in rats: Biochemical and histopathological assessment","volume":"95","author":"Yapca","year":"2023","journal-title":"An. Acad. Bras. Ci\u00eancias"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s40267-021-00853-y","article-title":"Metyrapone in Cushing\u2019s syndrome: A profile of its use","volume":"37","year":"2021","journal-title":"Drugs Ther. Perspect."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.reprotox.2015.12.006","article-title":"Inhibition of serotonin reuptake in the prepubertal rat ovary by fluoxetine and effects on ovarian functions","volume":"59","author":"Ayala","year":"2016","journal-title":"Reprod. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Joseph, D.N., and Whirledge, S. (2017). Stress and the HPA axis: Balancing homeostasis and fertility. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102224"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sheng, J.A., Bales, N.J., Myers, S.A., Bautista, A.I., Roueinfar, M., Hale, T.M., and Handa, R.J. (2021). The hypothalamic-pituitary-adrenal axis: Development, programming actions of hormones, and maternal-fetal interactions. Front. Behav. Neurosci., 14.","DOI":"10.3389\/fnbeh.2020.601939"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/rda.14444","article-title":"Pathogenesis of the crosstalk between reproductive function and stress in animals\u2014Part 1: Hypothalamo\u2013pituitary\u2013adrenal axis, sympatho\u2014Adrenomedullary system and kisspeptin","volume":"58","author":"Kaiser","year":"2023","journal-title":"Reprod. Domest. Anim."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1210\/endo.134.3.8119151","article-title":"Hypothalamic paraventricular nucleus lesions differentially affect serotonin-1A (5-HT1A) and 5-HT2 receptor agonist-induced oxytocin, prolactin, and corticosterone responses","volume":"134","author":"Bagdy","year":"1994","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1055\/s-2001-15416","article-title":"Effect of serotonin depletion by p-chlorophenylalanine on serum prolactin levels in estrogen-treated ovariectomized rats: Insights concerning the serotoninergic, dopaminergic and opioid systems","volume":"33","author":"Mallmann","year":"2001","journal-title":"Horm. Metab. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1515\/tjb-2018-0106","article-title":"Galactorrhea and hyperprolactinemia during vortioxetine use: Case report","volume":"44","author":"Ozkan","year":"2019","journal-title":"Turk. J. Biochem."},{"key":"ref_30","unstructured":"Al-Chalabi, M., Bass, A.N., and Alsalman, I. (2025). Physiology, Prolactin. StatPearls, StatPearls Publishing."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.yfrne.2014.02.001","article-title":"TIDAL WAVES: Network mechanisms in the neuroendocrine control of prolactin release","volume":"35","author":"Lyons","year":"2014","journal-title":"Front. Neuroendocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.neubiorev.2008.04.006","article-title":"Corticosteroid\u2013serotonin interactions in the neurobiological mechanisms of stress-related disorders","volume":"32","author":"Lanfumey","year":"2008","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s00213-002-1149-4","article-title":"Acute citalopram administration produces correlated increases in plasma and salivary cortisol","volume":"163","author":"Bhagwagar","year":"2002","journal-title":"Psychopharmacology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.neuroscience.2004.04.044","article-title":"Sex differences in behavioral, neurochemical and neuroendocrine effects induced by the forced swim test in rats","volume":"126","author":"Drossopoulou","year":"2004","journal-title":"Neuroscience"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Favero, V., Cremaschi, A., Falchetti, A., Gaudio, A., Gennari, L., Scillitani, A., Vescini, F., Morelli, V., Aresta, C., and Chiodini, I. (2021). Management and medical therapy of mild hypercortisolism. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111521"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0893-133X(95)00117-V","article-title":"Neuroendocrine effects of a 20-mg citalopram infusion in healthy males","volume":"14","author":"Seifritz","year":"1996","journal-title":"Neuropsychopharmacology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1365-2125.1994.tb04258.x","article-title":"Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans","volume":"37","author":"Skene","year":"1994","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.pnpbp.2017.07.008","article-title":"Effects of vortioxetine on biomarkers associated with glutamatergic activity in an SSRI insensitive model of depression in female rats","volume":"82","author":"Hlavacova","year":"2018","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Karunyam, B.V., Abdul Karim, A.K., Naina Mohamed, I., Ugusman, A., Mohamed, W.M., Faizal, A.M., Abu, M.A., and Kumar, J. (2023). Infertility and cortisol: A systematic review. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1147306"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Casillas, F., Betancourt, M., Ju\u00e1rez-Rojas, L., Ducolomb, Y., L\u00f3pez, A., \u00c1vila-Quintero, A., Zamora, J., Ommati, M.M., and Retana-M\u00e1rquez, S. (2021). Chronic stress detrimentally affects in vivo maturation in rat oocytes and oocyte viability at all phases of the estrous cycle. Animals, 11.","DOI":"10.3390\/ani11092478"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1080\/19396368.2023.2171822","article-title":"Chronic stress decreases fertility parameters in female rats","volume":"69","author":"Casillas","year":"2023","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.taap.2011.06.011","article-title":"Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol-treated female rats","volume":"255","author":"Trabace","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s11154-024-09900-1","article-title":"Could low prolactin levels after radiotherapy predict the onset of hypopituitarism?","volume":"25","author":"Mele","year":"2024","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e52720","DOI":"10.1590\/fst.52720","article-title":"Prolactin acts in the pathway of photoperiod regulating the reproduction of the Striped Hamsters","volume":"42","author":"Xue","year":"2021","journal-title":"Food Sci. Technol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1097\/WNF.0000000000000615","article-title":"Effect of Sertraline and Vortioxetine on Stress-Induced Brain Injury in Rats: Biochemical and Histopathological Evaluations","volume":"47","author":"Cim","year":"2024","journal-title":"Clin. Neuropharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Emir, I., Bulut, S., Suleyman, B., Mammadov, R., Yucel, N., Cicek, B., Yazici, G.N., Altuner, D., Gunay, M., and Suleyman, H. (2025). Pathogenesis-directed therapy of methylphenidate-induced oxidative heart damage in rats. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1503032"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1590\/s0102-865020180030000008","article-title":"The effect of metyrosine on oxidative gastric damage induced by ischemia\/reperfusion in rats. Biochemical and histopathological evaluation","volume":"33","author":"Bilgin","year":"2018","journal-title":"Acta Cir. Bras."},{"key":"ref_48","first-page":"1","article-title":"Cushing Sendromu ve Depresif Hastal\u0131klarda Metiraponun Yeni Perspektifleri","volume":"1","author":"Babayeva","year":"2024","journal-title":"Erzincan Binali Y\u0131ld\u0131r\u0131m \u00dcniversitesi Sa\u011fl\u0131k Bilim. Enstit\u00fcs\u00fc Derg."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Yilmaz, M., Suleyman, B., Mammadov, R., Altuner, D., Bulut, S., and Suleyman, H. (2023). The Role of Adrenaline, Noradrenaline, and Cortisol in the Pathogenesis of the Analgesic Potency, Duration, and Neurotoxic Effect of Meperidine. Medicina, 59.","DOI":"10.3390\/medicina59101793"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"114365","DOI":"10.1016\/j.bbr.2023.114365","article-title":"Vortioxetine improved negative and cognitive symptoms of schizophrenia in subchronic MK-801 model in rats","volume":"444","author":"Bozkurt","year":"2023","journal-title":"Behav. Brain Res."},{"key":"ref_51","first-page":"557","article-title":"Protective effects of vortioxetine in predator scent stress model of post-traumatic stress disorder in rats: Role on neuroplasticity and apoptosis","volume":"70","author":"Ozbeyli","year":"2019","journal-title":"J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc."},{"key":"ref_52","unstructured":"Li, Y., Pehrson, A.L., Sanchez, C., and Gulinello, M. (2015, January 16\u201320). Effects of Antidepressants in a Rat Model of Co-Morbid Cognitive Deficits and Depression-Like Behavior Induced by Ovariectomy. Proceedings of the 168th Annual Meeting of the American Psychiatric Association, Toronto, ON, Canada."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e361103","DOI":"10.1590\/acb361103","article-title":"Histomorphometric comparison of the corpus cavernosum of rats submitted to euthanasia with ketamine and xylazine or isoflurane","volume":"36","author":"Costa","year":"2021","journal-title":"Acta Cir\u00fargica Bras."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0009-8981(91)90067-M","article-title":"A simple method for determination of serum catalase activity and revision of reference range","volume":"196","author":"Goth","year":"1991","journal-title":"Clin. Chim. Acta"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1690\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T09:09:51Z","timestamp":1762852191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,7]]},"references-count":55,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ph18111690"],"URL":"https:\/\/doi.org\/10.3390\/ph18111690","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,7]]}}}