{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:32:07Z","timestamp":1792513927976,"version":"4.5.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100025154","name":"University of Sadat City","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100025154","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The present research was set out to delineate the protective and therapeutic potency of hesperidin (Hesp) versus cisplatin (Cis) against the deleterious consequences of Ehrlich ascites carcinoma (EAC) on the liver and the prospective mitigative effect of Hesp against Cis-mediated hepatotoxic side-effects. A total of 70 female mice were randomly assigned into control, Hesp, EAC, Hesp-protected, Hesp-treated, Cis-treated, and Cis\u2009+\u2009Hesp-treated groups. Mice inoculated with EAC cells exhibited significant reductions in the serum total protein and albumin levels, along with significant elevations of the serum aminotransferases, lactate dehydrogenase, amylase, and lipase activities, and alpha-fetoprotein level. A significant increment in malondialdehyde level concomitantly with significant declines in reduced glutathione concentration and catalase activity were also observed in the liver of EAC-bearing mice. Additionally, marked hepatic pathological changes as well as a strong Ki-67 expression and a weak caspase-3 expression in the neoplastic cells infiltrating hepatocytes were observed. In contrast, the administration of Hesp and\/or Cis to the EAC-bearing mice reversed, to varying degrees, the cytotoxic effects of EAC. Besides, Hesp minimized the harmful hepatic chemotherapeutic side-effects of Cis. Overall, Hesp could be a promising phytochemical against EAC-induced cytotoxicity with its potential to improve the antitumor efficacy of chemotherapeutic drugs and minimize their hepatic adverse side-effects.<\/jats:p>","DOI":"10.1038\/s41598-025-02442-9","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T08:27:45Z","timestamp":1751012865000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of Ehrlich ascites carcinoma in mice"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0040-1456","authenticated-orcid":false,"given":"Nahed","family":"Saleh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4081-4386","authenticated-orcid":false,"given":"Tamer","family":"Allam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-0317","authenticated-orcid":false,"given":"Reda M. S.","family":"Korany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7424-8151","authenticated-orcid":false,"given":"Abdelfattah M.","family":"Abdelfattah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5759-3087","authenticated-orcid":false,"given":"Ahmed M.","family":"Omran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9842-9777","authenticated-orcid":false,"given":"Mabrouk","family":"Attia Abd Eldaim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8461-7275","authenticated-orcid":false,"given":"Nermeen","family":"Borai El-Borai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"2442_CR1","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.3389\/fpls.2016.01667","volume":"7","author":"S Singh","year":"2016","unstructured":"Singh, S., Sharma, B., Kanwar, S. S. & Kumar, A. Lead phytochemicals for anticancer drug development. Front. Plant Sci. 7, 1667 (2016).","journal-title":"Front. Plant Sci."},{"issue":"5","key":"2442_CR2","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan, D. & Weinberg, R. A. Hallmarks of cancer. The next generation. Cell 144(5), 646\u2013674 (2011).","journal-title":"Cell"},{"issue":"1","key":"2442_CR3","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.cbi.2010.04.016","volume":"186","author":"N Bromberg","year":"2010","unstructured":"Bromberg, N. et al. Growth inhibition and pro-apoptotic activity of violacein in Ehrlich ascites tumor. Chem. Biol. Interact. 186(1), 43\u201352 (2010).","journal-title":"Chem. Biol. Interact."},{"issue":"1","key":"2442_CR4","first-page":"1","volume":"1","author":"TF Mutar","year":"2019","unstructured":"Mutar, T. F., Gazia, M. A., Salem, S. B., Hammed, E. H. & Tousson, E. Ehrlich ascites carcinoma bearing mice as model of human hepatocellular carcinoma. Asian J. Res. Rep. Hepatol. 1(1), 1\u20139 (2019).","journal-title":"Asian J. Res. Rep. Hepatol."},{"issue":"1","key":"2442_CR5","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jep.2010.03.010","volume":"129","author":"A Bala","year":"2010","unstructured":"Bala, A., Kar, B., Haldar, P. K., Mazumder, U. K. & Bera, S. Evaluation of anticancer activity of Cleome gynandra on Ehrlich\u2019s Ascites carcinoma treated mice. J. Ethnopharmacol. 129(1), 131\u2013134 (2010).","journal-title":"J. Ethnopharmacol."},{"issue":"9","key":"2442_CR6","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1080\/02772241003783703","volume":"92","author":"PK Haldar","year":"2010","unstructured":"Haldar, P. K. et al. Chemopreventive action of Indigofera aspalathoides against chemically induced carcinogenesis in mice. Toxicol. Environ. Chem. 92(9), 1749\u20131763 (2010).","journal-title":"Toxicol. Environ. Chem."},{"issue":"1","key":"2442_CR7","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1002\/tox.23016","volume":"36","author":"B Alotaibi","year":"2020","unstructured":"Alotaibi, B., Tousson, E., El-Masry, T. A., Altwaijry, N. & Saleh, A. Ehrlich ascites carcinoma as model for studying the cardiac protective effects of curcumin nanoparticles against cardiac damage in female mice. Environ. Toxicol. 36(1), 105\u2013113 (2020).","journal-title":"Environ. Toxicol."},{"issue":"9","key":"2442_CR8","doi-asserted-by":"publisher","first-page":"9236","DOI":"10.1007\/s11356-019-06528-6","volume":"27","author":"E Tousson","year":"2020","unstructured":"Tousson, E., Hafez, E., Abo Gazia, M. M., Salem, S. B. & Mutar, T. F. Hepatic ameliorative role of vitamin B17 against Ehrlich ascites carcinoma-induced liver toxicity. Environ. Sci. Pollut. Res. Int. 27(9), 9236\u20139246 (2020).","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"2442_CR9","doi-asserted-by":"publisher","first-page":"294","DOI":"10.3390\/ph15030294","volume":"15","author":"N Saleh","year":"2022","unstructured":"Saleh, N. et al. Protective and therapeutic efficacy of hesperidin versus cisplatin against Ehrlich ascites carcinoma-induced renal damage in mice. Pharmaceuticals 15, 294 (2022).","journal-title":"Pharmaceuticals"},{"issue":"1","key":"2442_CR10","doi-asserted-by":"publisher","first-page":"7","DOI":"10.13005\/bpj\/1608","volume":"12","author":"SA Aldossary","year":"2019","unstructured":"Aldossary, S. A. Review on pharmacology of cisplatin: Clinical use, toxicity and mechanism of resistance of cisplatin. Biomed. Pharmacol. J. 12(1), 7\u201315 (2019).","journal-title":"Biomed. Pharmacol. J."},{"key":"2442_CR11","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","volume":"740","author":"S Dasari","year":"2014","unstructured":"Dasari, S. & Tchounwou, P. B. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol. 740, 364\u2013378 (2014).","journal-title":"Eur. J. Pharmacol."},{"issue":"3","key":"2442_CR12","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1124\/pr.111.005637","volume":"64","author":"DW Shen","year":"2012","unstructured":"Shen, D. W., Pouliot, L. M., Hall, M. D. & Gottesman, M. M. Cisplatin resistance: A cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol. Rev. 64(3), 706\u2013721 (2012).","journal-title":"Pharmacol. Rev."},{"key":"2442_CR13","volume-title":"Biotechnology for Medicinal Plants","author":"ID Bhatt","year":"2013","unstructured":"Bhatt, I. D., Rawat, S. & Rawal, R. S. Antioxidants in medicinal plants. In Biotechnology for Medicinal Plants (eds Chandra, S. et al.) (Springer, 2013)."},{"key":"2442_CR14","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.foodchem.2015.09.072","volume":"196","author":"Z Zou","year":"2016","unstructured":"Zou, Z., Xi, W., Hu, Y., Nie, C. & Zhou, Z. Antioxidant activity of Citrus fruits. Food Chem. 196, 885\u2013896 (2016).","journal-title":"Food Chem."},{"key":"2442_CR15","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3390\/app12010029","volume":"12","author":"M Addi","year":"2022","unstructured":"Addi, M. et al. An overview of 575 bioactive flavonoids from citrus fruits. Appl. Sci. 12, 29 (2022).","journal-title":"Appl. Sci."},{"issue":"8","key":"2442_CR16","first-page":"4499","volume":"12","author":"N Singh","year":"2023","unstructured":"Singh, N. et al. Pharmacological and therapeutic potential of hesperidin-a comprehensive review eur. Eur. J. Org. Chem. 12(8), 4499\u20134537 (2023).","journal-title":"Eur. J. Org. Chem."},{"issue":"3","key":"2442_CR17","doi-asserted-by":"publisher","first-page":"478","DOI":"10.3390\/molecules25030478","volume":"25","author":"R Al-Rikabi","year":"2020","unstructured":"Al-Rikabi, R., Al-Shmgani, H., Dewir, Y. H. & El-Hendawy, S. In vivo and in vitro evaluation of the protective effects of hesperidin in lipopolysaccharide-induced inflammation and cytotoxicity of cell. Molecules 25(3), 478 (2020).","journal-title":"Molecules"},{"issue":"5","key":"2442_CR18","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1177\/1535370220903671","volume":"245","author":"V Aggarwal","year":"2020","unstructured":"Aggarwal, V. et al. Molecular mechanisms of action of hesperidin in cancer: Recent trends and advancements. Exp. Biol. Med. (Maywood) 245(5), 486\u2013497 (2020).","journal-title":"Exp. Biol. Med. (Maywood)"},{"issue":"30","key":"2442_CR19","doi-asserted-by":"publisher","first-page":"20042","DOI":"10.1021\/acsomega.1c03080","volume":"6","author":"AE Fazary","year":"2021","unstructured":"Fazary, A. E. et al. Bioactivity studies of hesperidin and XAV939. ACS Omega 6(30), 20042\u201320052 (2021).","journal-title":"ACS Omega"},{"issue":"15","key":"2442_CR20","first-page":"12","volume":"2","author":"VR Kumar","year":"2014","unstructured":"Kumar, V. R., Gouda, T. S., Sreelakshmi, S., Rajasekar, R. & Munawar, M. S. Protective potential of hesperidin against diethylnitrosamine induced hepatocarcinogenesis in rats. J. Drug Discov. Therapeut. 2(15), 12\u201316 (2014).","journal-title":"J. Drug Discov. Therapeut."},{"issue":"1","key":"2442_CR21","first-page":"305","volume":"9","author":"M Ali","year":"2018","unstructured":"Ali, M. et al. Evaluation of beneficial effects of Morinda Citrifolia L. in presence of cisplatin on Ehrlich\u2019s ascites carcinoma bearing mice. IJPSR 9(1), 305\u2013312 (2018).","journal-title":"IJPSR"},{"key":"2442_CR22","first-page":"692","volume-title":"Fundamentals of Clinical Chemistry","author":"NW Tietz","year":"1994","unstructured":"Tietz, N. W. Fundamentals of Clinical Chemistry 2nd edn, 692 (WB Saunders, 1994).","edition":"2"},{"key":"2442_CR23","first-page":"26","volume-title":"Clinical Guide to Laboratory Tests","author":"NW Tietz","year":"1990","unstructured":"Tietz, N. W. Clinical Guide to Laboratory Tests 2nd edn, 26\u201329 (WB Saunders, 1990).","edition":"2"},{"key":"2442_CR24","unstructured":"Young, D. S. Effects of drugs on clinical laboratory tests (3rd ed.) 3, 6\u201312 (1990)."},{"key":"2442_CR25","first-page":"268","volume-title":"Clinical Guide to Laboratory Tests","author":"NW Tietz","year":"1995","unstructured":"Tietz, N. W. Clinical Guide to Laboratory Tests 3rd edn, 268\u2013273 (WB Saunders, 1995).","edition":"3"},{"key":"2442_CR26","volume-title":"Effects of Diseases on Clinical Laboratory Tests","author":"DS Young","year":"2001","unstructured":"Young, D. S. Effects of Diseases on Clinical Laboratory Tests 4th edn. (AACC Press, 2001).","edition":"4"},{"issue":"3","key":"2442_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151069","volume":"11","author":"ES Jang","year":"2016","unstructured":"Jang, E. S. et al. Diagnostic performance of alpha-fetoprotein, protein induced by vitamin K absence, osteopontin, Dickkopf-1 and its combinations for hepatocellular carcinoma. PLoS ONE 11(3), e0151069 (2016).","journal-title":"PLoS ONE"},{"key":"2442_CR28","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","volume":"95","author":"H Ohkawa","year":"1979","unstructured":"Ohkawa, H., Ohishi, W. & Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95, 351 (1979).","journal-title":"Anal. Biochem."},{"key":"2442_CR29","first-page":"882","volume":"61","author":"E Beutler","year":"1963","unstructured":"Beutler, E., Duron, O. & Kelly, B. M. Improved method for the determination of blood glutathione. J. Lab. Clin. Med. 61, 882\u2013888 (1963).","journal-title":"J. Lab. Clin. Med."},{"key":"2442_CR30","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","volume":"105","author":"H Aebi","year":"1984","unstructured":"Aebi, H. Catalase in vitro. Methods Enzymol. 105, 121\u2013126 (1984).","journal-title":"Methods Enzymol."},{"key":"2442_CR31","volume-title":"Theory and Practice of Histological Techniques","author":"JD Bancroft","year":"2008","unstructured":"Bancroft, J. D. & Gamble, M. Theory and Practice of Histological Techniques 6th edn. (Churchill Livingstone, Elsevier, 2008).","edition":"6"},{"key":"2442_CR32","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s40543-024-00436-2","volume":"15","author":"MT Shaaban","year":"2024","unstructured":"Shaaban, M. T., Abdel-Hamid, M. S., Orabi, S. H., Korany, R. M. S. & Elbawab, R. H. Assessment of the antibacterial efficacy of silver nanoparticles-based Artemisia annua against methicillin-resistant Staphylococcus aureus-infected lung tissues in albino rats. J. Anal. Sci. Technol. 15, 25 (2024).","journal-title":"J. Anal. Sci. Technol."},{"issue":"3","key":"2442_CR33","first-page":"e13142","volume":"44","author":"AAA Abd El-Maksoud","year":"2020","unstructured":"Abd El-Maksoud, A. A. A. et al. Dietary solutions to dyslipidemia: Milk protein-polysaccharide conjugates as liver biochemical enhancers. J. Food Biochem. 44(3), e13142 (2020).","journal-title":"J. Food Biochem."},{"issue":"1","key":"2442_CR34","doi-asserted-by":"publisher","first-page":"2752","DOI":"10.1038\/s41598-024-52830-w","volume":"14","author":"NF Zaki","year":"2024","unstructured":"Zaki, N. F. et al. Zinc oxide resveratrol nanoparticles ameliorate testicular dysfunction due to levofloxacin-induced oxidative stress in rats. Sci. Rep. 14(1), 2752 (2024).","journal-title":"Sci. Rep."},{"issue":"1","key":"2442_CR35","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s13277-015-3774-7","volume":"37","author":"R Banjerdpongchai","year":"2016","unstructured":"Banjerdpongchai, R. et al. Hesperidin from Citrus seed induces human hepatocellular carcinoma HepG2 cell apoptosis via both mitochondrial and death receptor pathways. Tumour Biol. 37(1), 227\u2013237 (2016).","journal-title":"Tumour Biol."},{"key":"2442_CR36","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.indcrop.2015.07.051","volume":"76","author":"KP Devi","year":"2015","unstructured":"Devi, K. P. et al. Hesperidin: A promising anticancer agent from nature. Ind. Crops Prod. 76, 582\u2013589 (2015).","journal-title":"Ind. Crops Prod."},{"key":"2442_CR37","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.lfs.2014.12.030","volume":"124","author":"A Roohbakhsh","year":"2015","unstructured":"Roohbakhsh, A., Parhiz, H., Soltani, F., Rezaee, R. & Iranshahi, M. Molecular mechanisms behind the biological effects of hesperidin and hesperetin for the prevention of cancer and cardiovascular diseases. Life Sci. 124, 64\u201374 (2015).","journal-title":"Life Sci."},{"issue":"1","key":"2442_CR38","doi-asserted-by":"publisher","first-page":"5599","DOI":"10.1038\/s41598-018-23669-9","volume":"8","author":"S Mishra","year":"2018","unstructured":"Mishra, S. et al. Subcutaneous Ehrlich Ascites Carcinoma mice model for studying cancer-induced cardiomyopathy. Sci. Rep. 8(1), 5599 (2018).","journal-title":"Sci. Rep."},{"issue":"3","key":"2442_CR39","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.13005\/bpj\/2714","volume":"16","author":"J Hussein","year":"2023","unstructured":"Hussein, J., El-khayat, Z. & Farouk, H. Antitumor activity of selenium in Ehrlich ascites carcinoma bearing mice. Biomed. Pharmacol. J. 16(3), 1353\u20131364 (2023).","journal-title":"Biomed. Pharmacol. J."},{"key":"2442_CR40","doi-asserted-by":"crossref","unstructured":"Cowell, R.L. Preface. In Veterinary clinical pathology secrets. Elsevier Health Sciences, vii (Mosby, Saint Louis, 2004).","DOI":"10.1016\/B978-1-56053-633-8.50003-6"},{"issue":"1","key":"2442_CR41","first-page":"36","volume":"5","author":"VU Kiran","year":"2011","unstructured":"Kiran, V. U. et al. Antitumor activity of flavonoids against Ehrlich ascites carcinoma-induced mice. Int. J. Biomed. Pharm. Sci. 5(1), 36\u201339 (2011).","journal-title":"Int. J. Biomed. Pharm. Sci."},{"issue":"1","key":"2442_CR42","first-page":"58","volume":"2","author":"LL Huang","year":"2014","unstructured":"Huang, L. L., Xia, H. H. & Zhu, S. L. Ascitic fluid analysis in the differential diagnosis of ascites: Focus on cirrhotic ascites. J. Clin. Transl. Hepatol. 2(1), 58\u201364 (2014).","journal-title":"J. Clin. Transl. Hepatol."},{"key":"2442_CR43","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.cbi.2018.02.029","volume":"285","author":"TIK Donia","year":"2018","unstructured":"Donia, T. I. K., Gerges, M. N. & Mohamed, T. M. Amelioration effect of Egyptian sweet orange hesperidin on Ehrlich ascites carcinoma (EAC) bearing mice. Chem. Biol. Interact. 285, 76\u201384 (2018).","journal-title":"Chem. Biol. Interact."},{"issue":"1","key":"2442_CR44","doi-asserted-by":"publisher","first-page":"599","DOI":"10.12816\/0000596","volume":"52","author":"N Abdallah","year":"2013","unstructured":"Abdallah, N., Amien, N., Mohamed, M., Nada, A. & Mohamed, M. The protective value of hesperidin in mitigating the biochemical perturbations and trace element alterations induced by acrylonitrile in rats. Egypt. J. Hosp. Med. 52(1), 599\u2013607 (2013).","journal-title":"Egypt. J. Hosp. Med."},{"issue":"1","key":"2442_CR45","first-page":"11","volume":"2","author":"WG Hozayen","year":"2014","unstructured":"Hozayen, W. G., Seif, H. S. A. & Amin, S. Protective effects of ruitn and\/or hesperidin against doxorubicin-induced hepatotoxicity. Int. J. Clin. Nutr. 2(1), 11\u201317 (2014).","journal-title":"Int. J. Clin. Nutr."},{"key":"2442_CR46","volume-title":"Clinical Biochemistry of Domestic Animals","author":"JJ Kaneko","year":"1997","unstructured":"Kaneko, J. J., Harvey, J. W. & Bruss, M. L. Clinical Biochemistry of Domestic Animals 5th edn. (Academic Press, 1997).","edition":"5"},{"issue":"3","key":"2442_CR47","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1080\/10253890701248020","volume":"10","author":"RJ Adcock","year":"2007","unstructured":"Adcock, R. J. et al. Temporal relationships between plasma cortisol, corticosteroid-binding globulin (CBG), and the free cortisol index (FCI) in pigs in response to adrenal stimulation or suppression. Stress 10(3), 305\u2013310 (2007).","journal-title":"Stress"},{"issue":"6","key":"2442_CR48","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1055\/s-2007-980200","volume":"39","author":"DJ Torpy","year":"2007","unstructured":"Torpy, D. J. & Ho, J. T. Value of free cortisol measurement in systemic infection. Horm. Metab. Res. 39(6), 439\u2013444 (2007).","journal-title":"Horm. Metab. Res."},{"key":"2442_CR49","volume-title":"Fundamentals of Veterinary Clinical Pathology","author":"SL Stockham","year":"2002","unstructured":"Stockham, S. L. & Scott, M. A. Fundamentals of Veterinary Clinical Pathology (Lowa State Press, 2002)."},{"key":"2442_CR50","first-page":"3403972","volume":"1\u201312","author":"F Guo","year":"2018","unstructured":"Guo, F. et al. Grape seed proanthocyanidin extract inhibits human esophageal squamous cancerous cell line eca109 via the NF-\u03baB signaling pathway. Mediators Inflamm. 1\u201312, 3403972 (2018).","journal-title":"Mediators Inflamm."},{"key":"2442_CR51","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.biopha.2017.05.043","volume":"91","author":"D Medhat","year":"2017","unstructured":"Medhat, D. et al. Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations. Biomed. Pharmacother. 91, 1006\u20131016 (2017).","journal-title":"Biomed. Pharmacother."},{"key":"2442_CR52","first-page":"5162687","volume":"13","author":"MA Aldubayan","year":"2019","unstructured":"Aldubayan, M. A., Elgharabawy, R. M., Ahmed, A. S. & Tousson, E. Antineoplastic activity and curative role of avenanthramides against the growth of Ehrlich solid tumors in mice. Oxid. Med. Cell. Longev. 13, 5162687 (2019).","journal-title":"Oxid. Med. Cell. Longev."},{"issue":"1","key":"2442_CR53","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1002\/1097-0215(20001001)88:1<146::AID-IJC23>3.0.CO;2-I","volume":"88","author":"T Tanaka","year":"2000","unstructured":"Tanaka, T. et al. Suppression of azoxymethane-induced colon carcinogenesis in male F344 rats by mandarin juices rich in \u03b2-cryptoxanthin and hesperidin. Int. J. Cancer 88(1), 146\u2013150 (2000).","journal-title":"Int. J. Cancer"},{"issue":"12","key":"2442_CR54","doi-asserted-by":"publisher","first-page":"4757","DOI":"10.1021\/jf0502000","volume":"53","author":"PK Wilmsen","year":"2005","unstructured":"Wilmsen, P. K., Spada, D. S. & Salvador, M. Antioxidant activity of the flavonoid hesperidin in chemical and biological systems. J. Agric. Food Chem. 53(12), 4757\u20134761 (2005).","journal-title":"J. Agric. Food Chem."},{"issue":"8","key":"2442_CR55","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1007\/s00701-003-0073-7","volume":"145","author":"HK Rooprai","year":"2003","unstructured":"Rooprai, H. K., Christidou, M. & Pilkington, G. J. The potential for strategies using micronutrients and heterocyclic drugs to treat invasive gliomas. Acta. Neurochir. 145(8), 683\u2013690 (2003).","journal-title":"Acta. Neurochir."},{"issue":"2","key":"2442_CR56","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1002\/jsfa.1950","volume":"85","author":"JM Canadanovic-Brunet","year":"2005","unstructured":"Canadanovic-Brunet, J. M., Djilas, S. M., Cetkovic, G. S. & Tumbas, V. T. Free-radical scavenging activity of worm wood (Artemisia absinthium L.) extracts. J. Sci. Food Agric. 85(2), 265\u2013272 (2005).","journal-title":"J. Sci. Food Agric."},{"issue":"8","key":"2442_CR57","first-page":"1070","volume":"25","author":"M Gupta","year":"2004","unstructured":"Gupta, M., Mazumder, U. K., Kumar, R. S. & Kumar, T. S. Antitumor activity and antioxidant role of Bauhinia racemosa against Ehrlich ascites carcinoma in Swiss albino mice. Acta. Pharmacol. Sin. 25(8), 1070\u20131076 (2004).","journal-title":"Acta. Pharmacol. Sin."},{"issue":"2","key":"2442_CR58","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1254\/jphs.94.177","volume":"94","author":"M Gupta","year":"2004","unstructured":"Gupta, M., Mazumder, U. K., Kumar, R. S., Sivakumar, T. & Vamsi, M. L. Antitumor activity and antioxidant status of Caesalpinia bonducella against Ehrlich ascites carcinoma in Swiss albino mice. J. Pharmacol. Sci. 94(2), 177\u2013184 (2004).","journal-title":"J. Pharmacol. Sci."},{"issue":"5","key":"2442_CR59","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1039\/C6MD00618C","volume":"8","author":"EA Saad","year":"2017","unstructured":"Saad, E. A., Hassanien, M. M., El-Mezayen, H. A. & El- Menawy, N. M. Regression of murine Ehrlich ascites carcinoma using synthesized cobalt complex. Med. Chem. Commun. 8(5), 1103\u20131111 (2017).","journal-title":"Med. Chem. Commun."},{"issue":"1","key":"2442_CR60","doi-asserted-by":"publisher","first-page":"22","DOI":"10.4103\/jcrt.JCRT_862_16","volume":"17","author":"MD Jelic","year":"2021","unstructured":"Jelic, M. D., Mandic, A. D., Maricic, S. M. & Srdjenovic, B. U. Oxidative stress and its role in cancer. J. Cancer Res. Ther. 17(1), 22\u201328 (2021).","journal-title":"J. Cancer Res. Ther."},{"issue":"21\u201322","key":"2442_CR61","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/j.lfs.2008.03.002","volume":"82","author":"EJ Choi","year":"2008","unstructured":"Choi, E. J. Antioxidative effects of hesperetin against 7,12-dimethylbenz(a)anthracene-induced oxidative stress in mice. Life Sci. 82(21\u201322), 1059\u20131064 (2008).","journal-title":"Life Sci."},{"issue":"4","key":"2442_CR62","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/cdd.2014.216","volume":"22","author":"S Shalini","year":"2015","unstructured":"Shalini, S., Dorstyn, L., Dawar, S. & Kumar, S. Old, new and emerging functions of caspases. Cell Death Differ. 22(4), 526\u2013539 (2015).","journal-title":"Cell Death Differ."},{"issue":"1","key":"2442_CR63","doi-asserted-by":"publisher","first-page":"54","DOI":"10.21608\/blj.2018.47583","volume":"14","author":"FZ Mohammed","year":"2018","unstructured":"Mohammed, F. Z., Gurigis, A. A. & Gamal, A. Assessment of antiproliferative activity of Capparis spinosa L extract against Ehrlich ascites carcinoma in Swiss albino mice. Biochem. Lett. 14(1), 54\u201378 (2018).","journal-title":"Biochem. Lett."},{"key":"2442_CR64","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2020.103831","volume":"66","author":"MA Hashem","year":"2020","unstructured":"Hashem, M. A., Shoeeb, S. B. A., Abd-Elhakim, Y. M. & Mohamed, W. A. M. The antitumor activity of Arthrospira platensis and\/or cisplatin in a murine model of Ehrlich ascites carcinoma with hematinic and hepato-renal protective action. J. Funct. Foods 66, 103831 (2020).","journal-title":"J. Funct. Foods"},{"issue":"1","key":"2442_CR65","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.112423","volume":"399","author":"RG Aly","year":"2021","unstructured":"Aly, R. G., El-Enbaawy, M. I., Abd-El-Rahman, S. S. & Ata, N. S. Antineoplastic activity of Salmonella typhimurium outer membrane nanovesicles. Exp. Cell. Res. 399(1), 112423 (2021).","journal-title":"Exp. Cell. Res."},{"issue":"1\u20132","key":"2442_CR66","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.phymed.2007.07.061","volume":"15","author":"HJ Park","year":"2008","unstructured":"Park, H. J., Kim, M. J., Ha, E. & Chung, J. H. Apoptotic effect of hesperidin through caspase-3 activation in human colon cancer cells, SNU-C4. Phytomedicine 15(1\u20132), 147\u2013151 (2008).","journal-title":"Phytomedicine"},{"issue":"3","key":"2442_CR67","doi-asserted-by":"publisher","first-page":"e92128","DOI":"10.1371\/journal.pone.0092128","volume":"9","author":"R Bartoszewski","year":"2014","unstructured":"Bartoszewski, R. et al. Mangiferin has an additive effect on the apoptotic properties of hesperidin in Cyclopia sp. tea extracts. PLoS ONE 9(3), e92128 (2014).","journal-title":"PLoS ONE"},{"issue":"2","key":"2442_CR68","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.pharep.2015.09.007","volume":"68","author":"HA Omar","year":"2016","unstructured":"Omar, H. A. et al. Hesperidin alleviates cisplatin-induced hepatotoxicity in rats without inhibiting its antitumor activity. Pharmacol. Rep. 68(2), 349\u2013356 (2016).","journal-title":"Pharmacol. Rep."},{"issue":"2","key":"2442_CR69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.33552\/ANN.2020.07.000656","volume":"7","author":"FZ ELAblack","year":"2020","unstructured":"ELAblack, F. Z., Elgazzar, U. B. & Elsehily, A. Antitumor activity of novel azoles on ehrlich ascites carcinoma cells in mice. Arch. Neurol. Neurosci. 7(2), 1\u201311 (2020).","journal-title":"Arch. Neurol. Neurosci."},{"issue":"5","key":"2442_CR70","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22722","volume":"35","author":"EI Hassanen","year":"2021","unstructured":"Hassanen, E. I., Korany, R. M. S. & Bakeer, A. M. Cisplatin-conjugated gold nanoparticles-based drug delivery system for targeting hepatic tumors. J. Biochem. Mol. Toxicol. 35(5), e22722 (2021).","journal-title":"J. Biochem. Mol. Toxicol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02442-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02442-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02442-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T21:02:43Z","timestamp":1751403763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02442-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2442"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-02442-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]},"assertion":[{"value":"14 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study is reported in accordance with ARRIVE guidelines. Moreover, the research was performed in compliance with the Institutional Animal Care and Use Committee, Faculty of Veterinary Medicine, University of Sadat City, Egypt (Approval No. VUSC-003-1-21). The study follows the Guide for the Care and Use of Laboratory Animals 8th edition. Washington (DC): National Academies Press (US); 2011 and approved by IACUC of USC.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"20319"}}