{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:13:05Z","timestamp":1787029985563,"version":"build-2736575974"},"reference-count":128,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Umm Al-Qura University, Saudi Arabia","award":["25UQU4281227GSSR02"],"award-info":[{"award-number":["25UQU4281227GSSR02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Metronidazole (MTZ), a widely used antiamoebic and antibacterial drug, has been linked to male reproductive damage. The aim of this study was to investigate Olea europaea L. and Equisetum arvense L. ethanol extracts for the protection against testicular toxicity and male infertility caused by MTZ, and to characterize the underlying mechanisms. Forty-two male rats were divided into six groups. The animals in group 1 served as the controls and received a daily oral dose (1 mL) of the vehicle. The animals in group 2 received metronidazole at doses of 400 mg\/kg. Group 3 was treated with E. arvense extract at doses of 100 mg\/kg. Group 4 was treated with O. europaea leaf extract at doses of 400 mg\/kg. Group 5 was treated with metronidazole and E. arvense extract at doses of 400 and 100 mg\/kg, respectively. Group 6 was treated with metronidazole with O. europaea leaf extract at doses of 400 and 400 mg\/kg, respectively. The rats were given a daily oral dose of different treatments for 60 days, after which the animals were euthanized to study the histopathological and molecular changes in the testis and the sperm count in the epididymis. The testosterone levels, MDA levels, and GSH contents were also assessed in the rats in all groups. The findings revealed that the MTZ treatment caused a substantial increase in MDA levels and upregulated the NBN gene expression relative to the control. Moreover, the MTZ treatment produced significant reductions in the sperm count and viability, testosterone levels, and GSH content, and downregulated the INSL-3, STAR, HSD-3\u03b2, and CYP11A1 gene expression compared to the control. The adverse effects in testicular tissue were significantly reduced in rats given the O. europaea leaves and E. arvense treatment. The findings may show that MTZ can enhance testicular toxicity and infertility, but both plant extracts can prevent these harmful consequences.<\/jats:p>","DOI":"10.3390\/toxics14010042","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:30:32Z","timestamp":1767195032000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Protective Effects of Olea europaea L. Leaves and Equisetum arvense L. Extracts Against Testicular Toxicity Induced by Metronidazole Through Reducing Oxidative Stress and Regulating NBN, INSL-3, STAR, HSD-3\u03b2, and CYP11A1 Signaling Pathways"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0268-1498","authenticated-orcid":false,"given":"Asmaa A.","family":"Azouz","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa M.","family":"Ali","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0741-3954","authenticated-orcid":false,"given":"Mohamed","family":"Shaalan","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7033-7440","authenticated-orcid":false,"given":"Maha M.","family":"Rashad","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1674-4020","authenticated-orcid":false,"given":"Manal R.","family":"Bakeer","sequence":"additional","affiliation":[{"name":"Physiology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2181-7090","authenticated-orcid":false,"given":"Marwa Y.","family":"Issa","sequence":"additional","affiliation":[{"name":"Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8077-3668","authenticated-orcid":false,"given":"Sultan F.","family":"Kadasah","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, University of Bisha, Bisha 67714, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0804-2339","authenticated-orcid":false,"given":"Abdulmajeed Fahad","family":"Alrefaei","sequence":"additional","affiliation":[{"name":"Department of Biology, Jamoum University College, Umm Al Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3748-5905","authenticated-orcid":false,"given":"Rehab A.","family":"Azouz","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez-V\u00edas, G., Segarra, A.B., Ram\u00edrez-S\u00e1nchez, M., and Prieto, I. (2021). Olive oil and male fertility. Olives and Olive Oil in Health and Disease Prevention, Academic Press.","DOI":"10.1016\/B978-0-12-819528-4.00057-2"},{"key":"ref_2","first-page":"225","article-title":"Study on the reproductive organs and fertility of the male mice following administration of metronidazole","volume":"7","author":"Kumari","year":"2013","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.reprotox.2006.11.010","article-title":"Metronidazole-induced alterations in murine spermatozoa morphology","volume":"23","author":"Mudry","year":"2007","journal-title":"Reprod. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.intimp.2007.10.018","article-title":"Evaluation of immunosuppression induced by metronidazole in Balb\/c mice and human peripheral blood lymphocytes","volume":"8","author":"Fararjeh","year":"2008","journal-title":"Int. Immunopharmacol."},{"key":"ref_5","first-page":"303","article-title":"Histopathological and biochemical alterations of metronidazole-induced toxicity in male rats","volume":"9","author":"Oda","year":"2012","journal-title":"Glob. Vet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/toxres\/tfaa009","article-title":"Moringa oleifera leaves extract modulates toxicity, sperms alterations, oxidative stress, and testicular damage induced by tramadol in male rats","volume":"9","author":"Abd","year":"2020","journal-title":"Toxicol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Salmer\u00f3n-Manzano, E., Garrido-Cardenas, J.A., and Manzano-Agugliaro, F. (2020). Worldwide Research Trends on Medicinal Plants. Int. J. Environ. Res. Public. Health, 17.","DOI":"10.3390\/ijerph17103376"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.jep.2013.02.010","article-title":"Tyrosinase modulation by five Rwandese herbal medicines traditionally used for skin treatment","volume":"146","author":"Kamagaju","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_9","unstructured":"WHO (2015). Global Antimicrobial Resistance Surveillance System. Manual for Early Implementation, WHO."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100433","DOI":"10.1016\/j.phyplu.2023.100433","article-title":"Ethnomedicinal uses, phytochemistry and pharmacological study of Ocimum americanum L.: A review","volume":"3","author":"Luanda","year":"2023","journal-title":"Phytomed. Plus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100382","DOI":"10.1016\/j.phyplu.2022.100382","article-title":"Recent trend on Tetradenia riparia (Hochst.) Codd (Lamiaceae) for management of medical conditions","volume":"3","author":"Luanda","year":"2023","journal-title":"Phytomed. Plus"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e09586","DOI":"10.1016\/j.heliyon.2022.e09586","article-title":"A review on the potential of underutilized Blackjack (Biden pilosa) naturally occurring in sub-Saharan Africa","volume":"8","author":"Mtenga","year":"2022","journal-title":"Heliyon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117946","DOI":"10.1016\/j.carbpol.2021.117946","article-title":"Xylogalacturonan-enriched pectin from the fruit pulp of Adansonia digitata: Structural characterization and antidepressant-like effect","volume":"262","author":"Patova","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"200","DOI":"10.3390\/compounds2030017","article-title":"Ethnomedicinal, phytochemistry and antiviral potential of turmeric (Curcuma longa)","volume":"2","author":"Srivastava","year":"2022","journal-title":"Compounds"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27758","DOI":"10.3402\/fnr.v59.27758","article-title":"Ameliorating effect of olive oil on fertility of male rats fed on genetically modified soya bean","volume":"59","author":"Qahwaji","year":"2015","journal-title":"Food Nutr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/jpn.13617","article-title":"Effects of pomegranate peel and olive pomace supplementation on reproduction and oxidative status of rabbit doe","volume":"106","author":"Bakeer","year":"2022","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"52","DOI":"10.14715\/cmb\/2019.65.1.9","article-title":"Assessment of the anti-inflammatory, analgesic and sedative effects of oleuropein from Olea europaea L","volume":"65","author":"Mao","year":"2019","journal-title":"Cell Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"22100","DOI":"10.1007\/s11356-020-08371-6","article-title":"Olive leaf extract modulates glycerolinduced kidney and liver damage in rats","volume":"27","author":"Abugomaa","year":"2020","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_19","first-page":"e47127","article-title":"Olive leaves extract improved sperm quality and antioxidant status in the testis of rat exposed to rotenone","volume":"9","author":"Sarbishegi","year":"2017","journal-title":"Nephro.-Urol. Mon."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8487248","DOI":"10.1155\/2018\/8487248","article-title":"Evaluation of the protective effect of olive leaf extract on cisplatin-induced testicular damage in rats","volume":"2018","author":"Almeer","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s10341-019-00435-3","article-title":"Reproductive behavior and water use efficiency of olive trees (Olea europaea L. cv Konservolia) under deficit irrigation and mulching","volume":"61","author":"Gholami","year":"2019","journal-title":"Erwerbs-Obstbau"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jsps.2018.11.015","article-title":"Olive leaves extract attenuates type II diabetes mellitus-induced testicular damage in rats: Molecular and biochemical study","volume":"27","author":"Soliman","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_23","first-page":"131","article-title":"Equisetum arvense: Ethanopharmacological and phytochemical review with reference to osteoporosis single enzyme nanoparticles for application in humification and carbon sequestration process view project phytotherapeutics view project","volume":"1","author":"Badole","year":"2014","journal-title":"Int. J. Pharm. Sci. Health Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ijfoodmicro.2011.10.010","article-title":"Effect of Equisetum arvense and Stevia rebaudiana extracts on growth and mycotoxin production by Aspergillus flavus and Fusarium verticillioides in maize seeds as affected by water activity","volume":"153","author":"Garcia","year":"2012","journal-title":"Int. J. Food Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mas\u0142owski, M., Miedzianowska, J., Czylkowska, A., and Strzelec, K. (2020). Horsetail (Equisetum arvense) as a functional filler for natural rubber biocomposites. Materials, 13.","DOI":"10.3390\/ma13112526"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s12229-012-9113-4","article-title":"Biology and functional ecology of equisetum with emphasis on the giant horsetails","volume":"79","author":"Husby","year":"2013","journal-title":"Bot. Rev."},{"key":"ref_27","first-page":"457","article-title":"Therapeutic effect of Equisetum arvense L. on bone and scale biomarkers in female rats with induced osteoporosis","volume":"65","author":"Ibrahem","year":"2022","journal-title":"Egypt. J. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6658434","DOI":"10.1155\/2021\/6658434","article-title":"Phytochemistry and pharmacology of the genus Equisetum (Equisetaceae): A narrative review of the species with therapeutic potential for kidney diseases","volume":"2021","author":"Boeing","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_29","first-page":"618","article-title":"Effect of Equisetum arvense phenolic extract in treatment of Entamoeba histolytica infection","volume":"11","author":"Hasan","year":"2020","journal-title":"Syst. Rev. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1080\/13880209.2016.1230636","article-title":"Antibacterial, antioxidant and antiproliferative properties and zinc content of five south Portugal herbs","volume":"55","author":"Nunes","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_31","first-page":"93","article-title":"Protective effects of Equisetum arvense methanolic extract on sperm characteristics and in vitro fertilization potential in experimental diabetic mice: An experimental study","volume":"18","author":"Fajri","year":"2020","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.carbpol.2018.12.098","article-title":"Structural, rheological and antioxidant properties of pectins from Equisetum arvense L. and Equisetum sylvaticum L","volume":"1","author":"Patova","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2298\/CICEQ120327040K","article-title":"Total phenolic content, antioxidant and antimicrobial activity of Equisetum arvense L","volume":"19","author":"Kukric","year":"2013","journal-title":"Chem. Ind. Chem. Eng. Q."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3060525","DOI":"10.1155\/2018\/3060525","article-title":"Equisetum arvense L. Extract induces antibacterial activity and modulates oxidative stress, inflammation, and apoptosis in endothelial vascular cells exposed to hyperosmotic stress","volume":"2018","author":"Pallag","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.phrs.2003.10.002","article-title":"Antinociceptive and anti-inflammatory properties of the hydroalcoholic extract of stems from Equisetum arvense L. in mice","volume":"49","author":"Russi","year":"2004","journal-title":"Pharmacol. Res."},{"key":"ref_36","first-page":"146","article-title":"Equietum arvense: Pharmacology and phytochemistry\u2014A review","volume":"3","author":"Sandhu","year":"2010","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.fitote.2005.04.017","article-title":"Sedative and anticonvulsant effects of hydroalcoholic extract of Equisetum arvense","volume":"76","author":"Blanco","year":"2005","journal-title":"Fitoterapia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1089\/jmf.2008.0159","article-title":"Antioxidative and antiproliferative activities of different horsetail (Equisetum arvense L.) extracts","volume":"13","author":"Bogdanovic","year":"2010","journal-title":"J. Med. Food"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114744","DOI":"10.1016\/j.fct.2024.114744","article-title":"The mollifying effect of Sambucus nigra extract on StAR gene expression, oxidative stress, and apoptosis induced by fenpropathrin in male rats","volume":"189","author":"Nashed","year":"2024","journal-title":"Food Chem. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40659-025-00605-6","article-title":"Ameliorative effects of date palm kernel extract against fenpropathrin induced male reproductive toxicity","volume":"58","author":"Soliman","year":"2025","journal-title":"Biol. Res."},{"key":"ref_41","first-page":"555","article-title":"Epididymal semen analysis in testicular toxicity of doxorubicin in male albino Wistar rats and its amelioration with quercetin","volume":"7","author":"Divya","year":"2018","journal-title":"Pharma Innov. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"115274","DOI":"10.1016\/j.taap.2020.115274","article-title":"Nano selenium protects against deltamethrin-induced reproductive toxicity in male rats","volume":"408","author":"Hozyen","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_43","first-page":"882","article-title":"Improved method for the determination of blood glutathione","volume":"61","author":"Beutler","year":"1963","journal-title":"J. Lab. Clin. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2307\/2389604","article-title":"Oxyradical production as a pollution-mediated mechanism of toxicity in the common mussel, Mytilus edulis L., and other molluscs","volume":"4","author":"Livingstone","year":"1990","journal-title":"Funct. Ecol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1177\/0748233718791623","article-title":"Maternal exposure to di-n-butyl phthalate induces alterations of c-Myc gene, some apoptotic and growth related genes in pups\u2019 testes","volume":"34","author":"Rashad","year":"2018","journal-title":"Toxicol. Ind. Health"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s00441-022-03581-5","article-title":"Screening for polystyrene nanoparticle toxicity on kidneys of adult male albino rats using histopathological, biochemical, and molecular examination results","volume":"388","author":"Ahmed","year":"2022","journal-title":"Cell Tissue Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103911","DOI":"10.1016\/j.etap.2022.103911","article-title":"Exposure to Polystyrene nanoparticles induces liver damage in rat via induction of oxidative stress and hepatocyte apoptosis","volume":"94","author":"Yasin","year":"2022","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e22997","DOI":"10.1002\/jbt.22997","article-title":"Ameliorative effect of N-acetylcysteine on the testicular tissue of adult male albino rats after glyphosate-based herbicide exposure","volume":"36","author":"Hashim","year":"2022","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"250278","DOI":"10.4491\/eer.2025.278","article-title":"Counteracting titanium dioxide nanoparticle hepatotoxicity with ginseng: Modulation of oxidative stress, inflammation, and apoptosis in a rat model","volume":"31","author":"Abuzaied","year":"2026","journal-title":"Environ. Eng. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"117574","DOI":"10.1016\/j.taap.2025.117574","article-title":"Protective effects of zinc oxide nanoparticles against liver and kidney toxicity induced by oxymetholone, a steroid doping agent: Modulation of oxidative stress, inflammation, and gene expression in rats","volume":"505","author":"Abdelghafar","year":"2025","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Hesham, A., Abass, M., Abdou, H., Fahmy, R., Rashad, M.M., Abdallah, A.A., Mossallem, W., Rehan, I.F., Elnagar, A., and Zigo, F. (2023). Ozonated saline intradermal injection: Promising therapy for accelerated cutaneous wound healing in diabetic rats. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1283679"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"109008","DOI":"10.1016\/j.reprotox.2025.109008","article-title":"Ameliorative effect of curcumin loaded Nanoliposomes, A Promising bioactive formulation, against the DBP-induced testicular damage","volume":"137","author":"Bakeer","year":"2025","journal-title":"Reprod. Toxicol."},{"key":"ref_53","first-page":"2207","article-title":"Arsenate phytoremediation-linked genes in Egyptian rice cultivars as soil pollution DNA geno-sensor","volume":"15","author":"Rashad","year":"2018","journal-title":"Biosci. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/01480545.2022.2039180","article-title":"L-Carnitine alleviates hepatic and renal mitochondrial-dependent apoptotic progression induced by letrozole in female rats through modulation of Nrf-2, Cyt c and CASP-3 signaling","volume":"46","author":"Hassan","year":"2023","journal-title":"Drug Chem. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s11033-023-08991-4","article-title":"Physiological roles of propolis and red ginseng nanoplatforms in alleviating dexamethasone-induced male reproductive challenges in a rat model","volume":"51","author":"Aziz","year":"2024","journal-title":"Mol. Biol. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"114318","DOI":"10.1016\/j.jep.2021.114318","article-title":"Novel promising reproductive and metabolic effects of Cicer arietinum L. extract on letrozole induced polycystic ovary syndrome in rat model","volume":"278","author":"Ali","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s43088-022-00329-6","article-title":"Dysregulation of intraovarian redox status and steroidogenesis pathway in letrozole-induced PCOS rat model: A possible modulatory role of l-Carnitine","volume":"11","author":"Elmosalamy","year":"2022","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_58","unstructured":"Bancroft, J.D., and Gamble, M. (2013). Theories and Practice of Histological Techniques, Churchil Livingstone."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s41936-025-00495-w","article-title":"Effects of Propylparaben exposure on male reproductive function and fertility in CD-1 mice","volume":"86","author":"Hosny","year":"2025","journal-title":"J. Basic Appl. Zool"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Gr\u00fcndemann, C., Lengen, K., Sauer, B., Garcia-K\u00e4ufer, M., Zehl, M., and Huber, R. (2014). Equisetum arvense (common horsetail) modulates the function of inflammatory immunocompetent cells. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-283"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Serrano-Garc\u00eda, I., Olmo-Garc\u00eda, L., Polo-Meg\u00edas, D., Serrano, A., Le\u00f3n, L., de la Rosa, R., G\u00f3mez-Caravaca, A.M., and Carrasco-Pancorbo, A. (2022). Fruit Phenolic and Triterpenic Composition of Progenies of Olea europaea subsp. cuspidata, an Interesting Phytochemical Source to Be Included in Olive Breeding Programs. Plants, 11.","DOI":"10.3390\/plants11141791"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Toumi, K., \u015awi\u0105tek, \u0141., Boguszewska, A., Skalicka-Wo\u017aniak, K., and Bouaziz, M. (2023). Comprehensive Metabolite Profiling of Chemlali Olive Tree Root Extracts Using LC-ESI-QTOF-MS\/MS, Their Cytotoxicity, and Antiviral Assessment. Molecules, 28.","DOI":"10.3390\/molecules28124829"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Garcia-Aloy, M., Groff, N., Masuero, D., Nisi, M., Franco, A., Battelini, F., Vrhovsek, U., and Mattivi, F. (2020). Exploratory Analysis of Commercial Olive-Based Dietary Supplements Using Untargeted and Targeted Metabolomics. Metabolites, 10.","DOI":"10.3390\/metabo10120516"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Gazafroudi, N.K., Mail\u00e4nder, L.K., Daniels, R., Kammerer, D.R., and Stintzing, F.C. (2024). From Stem to Spectrum: Phytochemical Characterization of Five Equisetum Species and Evaluation of Their Antioxidant Potential. Molecules, 29.","DOI":"10.3390\/molecules29122821"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Abbattista, R., Ventura, G., Calvano, C.D., Cataldi, T.R.I., and Losito, I. (2021). Bioactive Compounds in Waste By-Products from Olive Oil Production: Applications and Structural Characterization by Mass Spectrometry Techniques. Foods, 10.","DOI":"10.3390\/foods10061236"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"127861","DOI":"10.1016\/j.foodchem.2020.127861","article-title":"Metabolome classification via GC\/MS and UHPLC\/MS of olive fruit varieties grown in Egypt reveal pickling process impact on their composition","volume":"339","author":"Fayek","year":"2021","journal-title":"Food Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.phytol.2014.12.020","article-title":"UHPLC-DAD-FLD and UHPLC-HRMS\/MS based metabolic profiling and characterization of different Olea europaea organs of Koroneiki and Chetoui varieties","volume":"11","author":"Michel","year":"2015","journal-title":"Phytochem. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"27539","DOI":"10.1038\/s41598-024-77860-2","article-title":"Impact of thermal processing on phytochemical profile and cardiovascular protection of Beta vulgaris L. in hyperlipidemic rats","volume":"14","author":"Mohsen","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.indcrop.2014.10.068","article-title":"Analysis of phenolic compounds in leaves from endemic trees from Madeira Island. A contribution to the chemotaxonomy of Laurisilva forest species","volume":"64","author":"Gouveia","year":"2015","journal-title":"Ind. Crops Prod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1055\/s-0033-1350823","article-title":"From olive drupes to olive oil. An HPLC-orbitrap-based qualitative and quantitative exploration of olive key metabolites","volume":"79","author":"Kanakis","year":"2013","journal-title":"Planta Medica"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/s41598-022-27119-5","article-title":"Comparative metabolic profiling of olive leaf extracts from twelve different cultivars collected in both fruiting and flowering seasons","volume":"13","author":"Kabbash","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"11542","DOI":"10.1021\/jf302896m","article-title":"Tentative identification of phenolic compounds in olive pomace extracts using liquid chromatography-tandem mass spectrometry with a quadrupole-quadrupole-time-of-flight mass detector","volume":"60","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Jeong, S.Y., Yu, H.S., Ra, M.J., Jung, S.M., Yu, J.N., Kim, J.C., and Kim, K.H. (2023). Phytochemical Investigation of Equisetum arvense and Evaluation of Their Anti-Inflammatory Potential in TNF\u03b1\/INF\u03b3-Stimulated Keratinocytes. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101478"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kritikou, E., Kalogiouri, N.P., Kolyvira, L., and Thomaidis, N.S. (2020). Target and Suspect HRMS Metabolomics for the Determination of Functional Ingredients in 13 Varieties of Olive Leaves and Drupes from Greece. Molecules, 25.","DOI":"10.3390\/molecules25214889"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"M\u0119czarska, K., Cyboran-Miko\u0142ajczyk, S., Solarska-\u015aciuk, K., Oszmia\u0144ski, J., Siejak, K., and Bonarska-Kujawa, D. (2025). Protective Effect of Field Horsetail Polyphenolic Extract on Erythrocytes and Their Membranes. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073213"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Gentile, L., Uccella, N.A., and Sivakumar, G. (2017). Soft-MS and computational mapping of oleuropein. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050992"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.supflu.2004.07.004","article-title":"Composition profile of horsetail (Equisetum giganteum L.) oleoresin: Comparing SFE and organic solvents extraction","volume":"33","author":"Michielin","year":"2005","journal-title":"J. Supercrit. Fluids"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S0890-6238(02)00052-7","article-title":"Effect of metronidazole, ipronidazole, and dibromochloropropane on rabbit and human sperm motility and fertility","volume":"16","author":"Foote","year":"2002","journal-title":"Reprod. Toxicol."},{"key":"ref_79","first-page":"1152","article-title":"Effect of metronidazole on spermatogenesis and FSH, LH and testosterone levels of pre-puberal rats","volume":"39","author":"Grover","year":"2001","journal-title":"Indian J. Exp. Biol."},{"key":"ref_80","unstructured":"Johnson, W.R., Gomes, W.R., and van Demark, N.H. (1977). Chemical agents affecting testicular function and male fertility. The Testis, Academic Press."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1289\/ehp.730659","article-title":"Possible role of the blood-testis barrier in dominant lethal testing","volume":"6","author":"Dixon","year":"1977","journal-title":"Environ. Health Perspect."},{"key":"ref_82","unstructured":"Plumb, D.C. (1999). Metronidazole. Veterinary Drug Handbook, Iowa State University Press. [3rd ed.]."},{"key":"ref_83","unstructured":"El-Ashmawy, I.M. (1988). Effect of Some Drugs on Male Fertility in the Rat. [Master\u2019s Thesis, Alexandria University]."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"110512","DOI":"10.1016\/j.ecoenv.2020.110512","article-title":"Bisphenol A affects the maturation and fertilization competence of spermatozoa","volume":"196","author":"Park","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"109827","DOI":"10.1016\/j.ecoenv.2019.109827","article-title":"Subcellular partitioning of cadmium and lead in Eisenia fetida and their effects to sperm count, morphology and apoptosis","volume":"187","author":"Sinkakarimi","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s40104-024-01031-6","article-title":"Patterns of alteration in boar semen quality from 9 to 37 months old and improvement by protocatechuic acid","volume":"15","author":"Hu","year":"2024","journal-title":"J. Animal Sci. Biotechnol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.theriogenology.2022.06.010","article-title":"Age-related endoplasmic reticulum stress represses testosterone synthesis via attenuation of the circadian clock in leydig cells","volume":"189","author":"Gao","year":"2022","journal-title":"Theriogenology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"110662","DOI":"10.1016\/j.ecoenv.2020.110662","article-title":"Exposure to PBDE47 affects mouse oocyte quality via mitochondria dysfunction-induced oxidative stress and apoptosis","volume":"198","author":"Sun","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.urology.2005.07.012","article-title":"What an andrologist\/urologist should know about free radicals and why","volume":"67","author":"Agarwal","year":"2006","journal-title":"Urology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0015-0282(16)43999-3","article-title":"Peroxidative breakdown of phospholipids in human spermatozoa, spermicidal properties of fatty acid peroxides, and protective action of seminal plasma","volume":"31","author":"Jones","year":"1979","journal-title":"Fertil. Steril."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1530\/ror.0.0020048","article-title":"Reactive oxygen species and sperm physiology","volume":"2","author":"Jiang","year":"1997","journal-title":"Rev. Reprod."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.fertnstert.2007.05.029","article-title":"Increase of oxidative stress in human sperm with lower motility","volume":"89","author":"Kao","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1472-6483(10)61730-0","article-title":"Oxidative stress in the male germ line and its role in the aetiology of male infertility and genetic disease","volume":"7","author":"Aitken","year":"2003","journal-title":"Reprod. Biomed. Online"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1021\/tx700210j","article-title":"Oxidative stress and neurotoxicity","volume":"21","author":"Sayre","year":"2007","journal-title":"Chem. Res. Toxicol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s10787-016-0274-3","article-title":"Redefining the role of peripheral LPS as a neuroinflammatory agent and evaluating the role of hydrogen sulphide through metformin intervention","volume":"24","author":"Tiwari","year":"2016","journal-title":"Inflammopharmacology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.neuro.2022.06.006","article-title":"Selenium nanoparticles impart robust neuroprotection against deltamethrin-induced neurotoxicity in male rats by reversing behavioral alterations, oxidative damage, apoptosis, and neuronal loss","volume":"91","author":"Khalil","year":"2022","journal-title":"NeuroToxicology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"327","DOI":"10.29261\/pakvetj\/2023.023","article-title":"Bovine papillomatosis: A serological, hematobiochemical, ultrastructural and immunohistochemical investigation in cattle","volume":"43","author":"Khattab","year":"2023","journal-title":"Pak. Vet. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/are.14884","article-title":"Buprofezin toxication implicates health hazards in Nile tilapia (Oreochromis niloticus)","volume":"52","author":"Azouz","year":"2021","journal-title":"Aquac. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.foodres.2015.09.011","article-title":"Phenolic compounds in olive leaves: Analytical determination, biotic and abiotic influence, and health benefits","volume":"77","author":"Talhaoui","year":"2015","journal-title":"Food Res. Int."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.foodchem.2016.06.001","article-title":"Phenolic content and antioxidant activity of olive by-products and antioxidant film containing olive leaf extract","volume":"212","author":"Moudache","year":"2016","journal-title":"Food Chem."},{"key":"ref_101","first-page":"205","article-title":"Oleuropein protects against ethanol-induced oxidative stress and modulates sperm quality in the rat testis","volume":"5","author":"Alirezaei","year":"2012","journal-title":"Med. J. Nutr. Metab."},{"key":"ref_102","first-page":"293","article-title":"The effect of a hydro-alcoholic extract of olive fruit on reproductive argons in male sprague-dawley rat","volume":"11","author":"Najafizadeh","year":"2013","journal-title":"Iran J. Reprod. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"101","DOI":"10.9734\/jpri\/2021\/v33i34A31829","article-title":"Equisetum arvense L. Extract Ameliorates Oxidative Stress, Inflammation and Testicular Injury Induced by Methotrexate in Male Rats","volume":"33","author":"Alahmadi","year":"2021","journal-title":"J. Pharm. Res. Int."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1055\/s-0043-123075","article-title":"In vitro anti-inflammatory effects of Equisetum arvense are not solely mediated by silica","volume":"84","author":"Steinborn","year":"2018","journal-title":"Planta Med."},{"key":"ref_105","first-page":"176","article-title":"Effect of Equisetum arvense extract on bone mineral density in Wistar rats via digital radiography","volume":"10","author":"Arbabzadegan","year":"2019","journal-title":"Casp. J. Intern. Med."},{"key":"ref_106","first-page":"11","article-title":"Testicular toxicity of metronidazole: Histopathological and biochemical evidence","volume":"9","author":"Farag","year":"2012","journal-title":"Toxicol. Rep."},{"key":"ref_107","first-page":"476","article-title":"Reproductive toxicity of metronidazole in male rats","volume":"5","author":"Baligar","year":"2013","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Hassan, A.A., Bel Hadj Salah, K., Fahmy, E.M., Mansour, D.A., Mohamed, S.A.M., Abdallah, A.A., Ashkan, M.F., Majrashi, K.A., Melebary, S.J., and El-Sheikh, E.-S.A. (2022). Olive leaf extract attenuates chlorpyrifos-induced neuro-and reproductive toxicity in male albino rats. Life, 12.","DOI":"10.3390\/life12101500"},{"key":"ref_109","first-page":"113067","article-title":"Antioxidant potential of Equisetum arvense in mitigating reproductive toxicity","volume":"260","author":"Shalaby","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_110","unstructured":"B\u0103d\u0103r\u0103u, A.S., Aprotosoaie, A.C., Gille, E., and Miron, A. (2014). Flavonoid and phenolic content of Equisetum arvense L. and their contribution to the antioxidant activity. BMC Complement. Altern. Med., 14."},{"key":"ref_111","first-page":"201","article-title":"Characterization of silica accumulation and distribution in Equisetum arvense","volume":"136","author":"Lee","year":"2023","journal-title":"J. Plant Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1177\/0960327119867755","article-title":"Thiamine deficiency and oxidative stress induced by prolonged metronidazole therapy can explain its side effects of neurotoxicity and infertility in experimental animals: Effect of grapefruit co-therapy","volume":"39","author":"Hassan","year":"2020","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1071\/RD16174","article-title":"Rosmarinic acid reverses the effects of metronidazole-induced infertility in male albino rats","volume":"29","author":"Shraideh","year":"2017","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3923\/pjbs.2012.224.230","article-title":"Antifertility potentials of metronidazole in male Wistar rats","volume":"15","author":"Ligha","year":"2012","journal-title":"Pak. J. Biol. Sci."},{"key":"ref_115","first-page":"69","article-title":"Effect of metronidazole on spermatogenesis, plasma gonadotrophins and testosterone in rats","volume":"15","author":"Sohrabi","year":"2007","journal-title":"Iran J. Reprod. Med."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Monageng, E., Offor, U., Takalani, N.B., Mohlala, K., and Opuwari, C.S. (2023). A Review on the Impact of Oxidative Stress and Medicinal Plants on Leydig Cells. Antioxidants, 12.","DOI":"10.3390\/antiox12081559"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41435-021-00139-3","article-title":"Revisiting steroidogenesis and its role in immune regulation with the advanced tools and technologies","volume":"22","author":"Chakraborty","year":"2021","journal-title":"Genes. Immun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/molehr\/gap025","article-title":"Regulation of the steroidogenic acute regulatory protein gene expression: Present and future perspectives","volume":"15","author":"Manna","year":"2009","journal-title":"Mol. Hum. Reprod."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"153208","DOI":"10.1016\/j.tox.2022.153208","article-title":"Alterations in reproductive parameters and steroid biosynthesis induced by nickel oxide nanoparticles in male rats: The ameliorative eFfect of hesperidin","volume":"473","author":"Noshy","year":"2022","journal-title":"Toxicology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.cbi.2019.02.027","article-title":"Endocrine disruptors of inhibiting testicular 3\u03b2-hydroxysteroid dehydrogenase","volume":"303","author":"Zhang","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_121","first-page":"1339","article-title":"Oxidative effect of metronidazole on the testis of Wistar rats","volume":"5","author":"Ligha","year":"2011","journal-title":"Aust. J. Basic Appl. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"304","DOI":"10.4103\/0253-7613.157129","article-title":"Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse","volume":"47","author":"Kumari","year":"2015","journal-title":"Indian J. Pharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/toxres\/tfac009","article-title":"Cerium oxide nanoparticles attenuate the renal injury induced by cadmium chloride via improvement of the NBN and Nrf2 gene expressions in rats","volume":"11","author":"Bashandy","year":"2022","journal-title":"Toxicol. Res."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Ivell, R., Heng, K., and Anand-Ivell, R. (2014). Insulin-like factor 3 and the HPG axis in the male. Front. Endocrinol., 5.","DOI":"10.3389\/fendo.2014.00006"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.foodchem.2004.04.016","article-title":"Antioxidative activities of water extract and ethanol extract from field horsetail (Tsukushi) Equisetum arvense L","volume":"91","author":"Nagai","year":"2005","journal-title":"Food Chem."},{"key":"ref_126","first-page":"41","article-title":"Phenolic content, antioxidant activity and effect on collagen synthesis of a traditional wound healing polyherbal formula","volume":"25","author":"Alexandru","year":"2015","journal-title":"Studia Univ."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Bakeer, M.R., Rashad, M.M., Azouz, A.A., Azouz, R.A., Alrefaei, A.F., Kadasah, S.F., Shaalan, M., Ali, A.M., Issa, M.Y., and El-Samanoudy, S.I. (2025). Molecular, Physiological, and Histopathological Insights into the Protective Role of Equisetum arvense and Olea europaea Extracts Against Metronidazole-Induced Pancreatic Toxicity. Life, 15.","DOI":"10.3390\/life15121907"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00775-015-1320-0","article-title":"Isolation of a wide range of minerals from a thermally treated plant: Equisetum arvense, a Mare\u2019s tale","volume":"21","author":"Rinck","year":"2016","journal-title":"J. Biol. Inorg. Chem."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/1\/42\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:05:36Z","timestamp":1767197136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/1\/42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,30]]},"references-count":128,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["toxics14010042"],"URL":"https:\/\/doi.org\/10.3390\/toxics14010042","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,30]]}}}