{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:08:56Z","timestamp":1784542136354,"version":"3.55.0"},"reference-count":81,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to evaluate the general, hepatoprotective and renoprotective effects of amifostine (AMI) in rats treated with a large, single dose of doxorubicin (DOX), assessed at 7 and 56 days after administration. Rats were divided into six experimental groups: Control (0.9% NaCl intraperitoneally (ip)), amifostine (AMI300, 300 mg\/kg (ip)), doxorubicin (DOX6, 6 mg\/kg (ip)), doxorubicin (DOX10, 10 mg\/kg (ip)), doxorubicin (DOX6, 6 mg\/kg (ip)) + amifostine (AMI300, 300 mg\/kg (ip) 30 min before DOX6), and doxorubicin (DOX10, 10 mg\/kg (ip)) + amifostine (AMI300, 300 mg\/kg (ip) 30 min before DOX10). Absolute liver and kidney weights were significantly increased in AMI300 + DOX6-treated animals compared to DOX6 only on day 56. In the group of DOX10-treated rats, AMI300 significantly prevented changes in the number of white blood cells during the four weeks after treatment. The severity of hepatic and renal injuries in the DOX6-treated groups was also significantly less in rats pretreated with AMI300 on day 56 (p &lt; 0.01). Our results indicate that hepatic and renal protection significantly contribute to the successful use of AMI against DOX-induced subacute toxicity in rats.<\/jats:p>","DOI":"10.3390\/ijms27146419","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:32:54Z","timestamp":1784539974000},"page":"6419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Amifostine Attenuates Doxorubicin-Induced Subacute Hepatic and Renal Toxicity in Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5137-2638","authenticated-orcid":false,"given":"Vesna","family":"Ja\u0107evi\u0107","sequence":"first","affiliation":[{"name":"Department of Experimental Toxicology and Pharmacology, National Poison Control Centre, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia"},{"name":"Department for Pharmacological Science, Medical Faculty of the Military Medical Academy, University of Defence in Belgrade, Crnotravska 17, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-0762","authenticated-orcid":false,"given":"Viktorija","family":"Dragojevi\u0107-Simi\u0107","sequence":"additional","affiliation":[{"name":"Department for Pharmacological Science, Medical Faculty of the Military Medical Academy, University of Defence in Belgrade, Crnotravska 17, 11000 Belgrade, Serbia"},{"name":"Centre for Clinical Pharmacology, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8014-3121","authenticated-orcid":false,"given":"Jelica","family":"Gruji\u0107-Milanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Research, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0493-8525","authenticated-orcid":false,"given":"Silva","family":"Dobri\u0107","sequence":"additional","affiliation":[{"name":"Vojnosanitetski Pregled, Medical Faculty of the Military Medical Academy, University of Defence in Belgrade, Crnotravska 17, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dubravko","family":"Bokonji\u0107","sequence":"additional","affiliation":[{"name":"Department of Experimental Toxicology and Pharmacology, National Poison Control Centre, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoran","family":"Milovanovi\u0107","sequence":"additional","affiliation":[{"name":"Special Police Unit, Police Department of the City of Belgrade, Ministry of Interior, Trebevi\u0107ka 12\/A, 11030 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7688-1201","authenticated-orcid":false,"given":"Sladjan","family":"Milanovi\u0107","sequence":"additional","affiliation":[{"name":"Department for Biomechanics, Biomedical Engineering and Physics of Complex Systems, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0824-951X","authenticated-orcid":false,"given":"Radoje","family":"Simi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Mother and Child Health Care of Serbia \u201cDr Vukan \u010cupi\u0107\u201d, University of Belgrade, Radoja Daki\u0107a 6-8, 11000 Belgrade, Serbia"},{"name":"Medical Faculty, University of Belgrade, dr. Suboti\u0107a 8, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111708","DOI":"10.1016\/j.biopha.2021.111708","article-title":"Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management","volume":"139","author":"Rawat","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.54457\/DR.202402015","article-title":"Multifaced anticancer potential of doxorubicin: Spotlight on breast cancer","volume":"5","author":"Swain","year":"2025","journal-title":"Dis. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s13346-024-01648-0","article-title":"A comprehensive review on doxorubicin: Mechanisms, toxicity, clinical trials, combination therapies and nanoformulations in breast cancer","volume":"15","author":"Bisht","year":"2025","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"119527","DOI":"10.1016\/j.lfs.2021.119527","article-title":"A comprehensive review on time-tested anticancer drug doxorubicin","volume":"278","author":"Sritharan","year":"2021","journal-title":"Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4161","DOI":"10.1002\/cncr.33804","article-title":"Intensity-modulated radiation therapy and doxorubicin in thyroid cancer: A prospective phase 2 trial","volume":"15","author":"Romesser","year":"2021","journal-title":"Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bhutani, V., Varzideh, F., Wilson, S., Kansakar, U., Jankauskas, S.S., and Santulli, G. (2025). Doxorubicin-induced cardiotoxicity: A comprehensive update. J. Cardiovasc. Dev. Dis., 30, Erratum in J. Cardiovasc. Dev. Dis.\u00a02025, 12, 242.","DOI":"10.3390\/jcdd12070242"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1080\/15569543.2021.1912099","article-title":"Toxic effects and molecular mechanism of doxorubicin on different organs\u2014An update","volume":"41","author":"Renu","year":"2022","journal-title":"Toxin Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"164","DOI":"10.18632\/aging.204466","article-title":"Doxorubicin-induced ROS-dependent HIF1\u03b1 activation mediates blockage of IGF1R survival signalling by IGFBP3 promotes cardiac apoptosis","volume":"3","author":"Wen","year":"2023","journal-title":"Aging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"760","DOI":"10.7150\/ijbs.65258","article-title":"Underlying the mechanisms of doxorubicin-induced acute cardiotoxicity: Oxidative stress and cell death","volume":"18","author":"Kong","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vitale, R., Marzocco, S., and Popolo, A. (2024). Role of oxidative stress and inflammation in doxorubicin-induced cardiotoxicity: A brief account. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202405.1681.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s12012-022-09721-1","article-title":"Doxorubicin-induced cardiotoxicity: An overview on pre-clinical therapeutic approaches","volume":"22","author":"Sheibani","year":"2022","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Afonso, A.I., Amaro-Leal, \u00c2., Machado, F., Rocha, I., and Geraldes, V. (2023). Doxorubicin dose-dependent impact on physiological balance\u2014A holistic approach in a rat model. Biology, 12.","DOI":"10.3390\/biology12071031"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.2298\/VSP110905041D","article-title":"Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats","volume":"70","year":"2013","journal-title":"Vojnosanit. Pregl."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.lfs.2018.03.023","article-title":"Toxicity of Doxorubicin (Dox) to different experimental organ systems","volume":"200","author":"Pugazhendhi","year":"2018","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2174\/1874325000802010115","article-title":"Effect of dexrazoxane and amifostine on the vertebral bone quality of doxorubicin treated male rats","volume":"2","author":"Mwale","year":"2008","journal-title":"Open Orthop. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/BF00262774","article-title":"Epirubicin and doxorubicin comparative metabolism and pharmacokinetics","volume":"21","author":"Camaggi","year":"1988","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112373","DOI":"10.1016\/j.biopha.2021.112373","article-title":"pH-sensitive doxorubicin-tocopherol succinate prodrug encapsulated in docosahexaenoic acid-based nanostructured lipid carriers: An effective strategy to improve pharmacokinetics and reduce toxic effects","volume":"144","author":"Paiyabhroma","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"117599","DOI":"10.1016\/j.lfs.2020.117599","article-title":"New molecular and biochemical insights of doxorubicin-induced hepatotoxicity","volume":"250","author":"Prasanna","year":"2020","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.freeradbiomed.2020.10.303","article-title":"Xanthine oxidase inhibition attenuates doxorubicin-induced cardiotoxicity in mice","volume":"162","author":"Tanaka","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Karanovic, D., Grujic-Milanovic, J., Miloradovic, Z., Ivanov, M., Jovovic, D.J., Vajic, U.J., Zivotic, M., Markovic-Lipkovski, J., and Mihailovic-Stanojevic, N. (2016). Effects of single and combined losartan and tempol treatments on oxidative stress, kidney structure and function in spontaneously hypertensive rats with early course of proteinuric nephropathy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161706"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/j.2040-4603.2013.tb00507.x","article-title":"Apoptosis and necrosis in the liver","volume":"3","author":"Guicciardi","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1006\/phrs.2000.0769","article-title":"The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats","volume":"43","author":"Saad","year":"2000","journal-title":"Pharmacol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1124\/pr.56.2.6","article-title":"Anthracyclines: Molecular advances and pharmacologic development in antitumor activity and cardiotoxicity","volume":"56","author":"Minoti","year":"2004","journal-title":"Pharmacol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113373","DOI":"10.1016\/j.intimp.2024.113373","article-title":"Molecular signalling pathways in doxorubicin-induced nephrotoxicity and potential therapeutic agents","volume":"144","author":"Lu","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_25","first-page":"819","article-title":"Anti-inflammatory activity of fullerenol C60(OH)24 nano-particles in a model of acute inflammation in rats","volume":"6","author":"Jacevic","year":"2011","journal-title":"Dig. J. Nanomater. Bios"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.yexmp.2017.03.005","article-title":"Fullerenol nanoparticles prevents doxorubicin-induced acute hepatotoxicity in rats","volume":"102","author":"Jacevic","year":"2017","journal-title":"Exp. Mol. Path"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.2337\/diab.43.11.1271","article-title":"Tumor necrosis factor alpha: A key component of the obesity-diabetes link","volume":"43","author":"Hotamisligil","year":"1994","journal-title":"Diabetes"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1158\/1078-0432.CCR-06-2082","article-title":"Reactive oxygen species: A breath of life or death?","volume":"1","author":"Fruehauf","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111308","DOI":"10.1016\/j.biopha.2021.111308","article-title":"Apigenin ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation","volume":"137","author":"Wu","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jphs.2020.10.002","article-title":"Alleviation of the doxorubicin-induced nephrotoxicity by fasudil in vivo and in vitro","volume":"145","author":"Xiang","year":"2021","journal-title":"J. Pharmacol. Sci."},{"key":"ref_31","first-page":"1142","article-title":"Reduced progression of Adriamycin nephropathy in spontaneously hypertensive rats treated by losartan","volume":"24","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2298\/SARH0204073J","article-title":"Slowing progression of chronic renal insufficiency with captopril in rats with spontaneous arterial hypertension and adriamycin nephropathy","volume":"130","year":"2002","journal-title":"Srp. Arh. Celok. Lek."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Xing, W., Wen, C., Wang, D., Shao, H., Liu, C., He, C., and Olatunji, O.J. (2022). Cardiorenal protective effect of costunolide against doxorubicin-induced toxicity in rats by modulating oxidative stress, inflammation and apoptosis. Molecules, 27.","DOI":"10.3390\/molecules27072122"},{"key":"ref_34","first-page":"169","article-title":"Amifostine protection against doxorubicin cardiotoxicity in rats","volume":"15","author":"Dobric","year":"2004","journal-title":"Anti-Cancer Drugs"},{"key":"ref_35","first-page":"6423","article-title":"Amifostine protects against early but not late toxic effects of doxorubicin in infant rats","volume":"1","author":"Jahnukainen","year":"2001","journal-title":"Cancer Res."},{"key":"ref_36","first-page":"738","article-title":"Amifostine: The first selective-target and broad-spectrum radioprotector","volume":"12","author":"Kouvaris","year":"2007","journal-title":"Oncology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1053\/sonc.2002.37355","article-title":"Preclinical studies on the radioprotective efficacy and pharmacokinetics of subcutaneously administered amifostine","volume":"29","author":"Cassatt","year":"2002","journal-title":"Sem. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1097\/00005537-200409000-00030","article-title":"High-dose cisplatin with amifostine: Ototoxicity and pharmacokinetics","volume":"114","author":"Ekborn","year":"2004","journal-title":"Laryngoscope"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ja\u0107evi\u0107, V., Dragojevi\u0107-Simi\u0107, V., Tatomirovi\u0107, \u017d., Dobri\u0107, S., Bokonji\u0107, D., Kova\u010devi\u0107, A., Nepovimova, E., Vali\u0161, M., and Ku\u010da, K. (2018). The efficacy of amifostine against multiple-dose doxorubicin-induced toxicity in rats. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082370"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s42826-024-00194-7","article-title":"Age-related changes in hematological and biochemical profiles of Wistar rats","volume":"26","author":"Patel","year":"2024","journal-title":"Lab. Anim. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.jab.2016.05.004","article-title":"Effects of fullerenol nanoparticles and amifostine on radiation-induced tissue damages: Histopathological analysis","volume":"14","author":"Jacevic","year":"2016","journal-title":"J. Appl. Biomed."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1089\/ars.2012.4795","article-title":"Oxidative stress, redox signalling, and metal chelation in anthracycline cardiotoxicity and pharmacological cardioprotection","volume":"18","author":"Sterba","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1600-0773.1994.tb00330.x","article-title":"Cardiotoxicity of doxorubicin: Effects of drugs inhibiting the release of vasoactive substances","volume":"75","author":"Rossi","year":"1994","journal-title":"Pharmacol. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Van Asbroeck, B., Kr\u00fcger, D.N., Van den Bogaert, S., Dombrecht, D., Bosman, M., Van Craenenbroeck, E.M., Guns, P.-J., and van Breda, E. (2025). Distinct Impact of Doxorubicin on Skeletal Muscle and Fat Metabolism in Mice: Without Dexrazoxane Effect. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031177"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"118859","DOI":"10.1016\/j.biopha.2025.118859","article-title":"A comparative study of idarubicin and doxorubicin in a chemically-induced in vivo mouse model for hepatocellular carcinoma","volume":"193","author":"Kopsida","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1080\/10717544.2019.1591544","article-title":"Doxorubicin-loaded red blood cells reduced cardiac toxicity and preserved anticancer activity","volume":"26","author":"Lucas","year":"2019","journal-title":"Drug Deliv."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1016\/j.biocel.2012.06.010","article-title":"The opposite effects of doxorubicin on bone marrow stem cells versus breast cancer stem cells depend on glucosylceramide synthase","volume":"44","author":"Bhinge","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11","DOI":"10.21608\/absb.2021.72920.1111","article-title":"Biochemical and hemological changes against doxorubicin-induced toxicity in rats","volume":"32","author":"Thabit","year":"2021","journal-title":"Al-Azhar Bull. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1191\/0960327102ht311oa","article-title":"Comparative study of chronic toxic effects of daunorubicin and doxorubicin in rabbits","volume":"21","author":"Hrdina","year":"2002","journal-title":"Human Exp. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"096","DOI":"10.30574\/wjarr.2021.9.3.0084","article-title":"Prevention of doxorubicin-induced haematotoxicity by turmeric in Wistar rats","volume":"9","author":"Isirima","year":"2021","journal-title":"World J. Adv. Res. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.3324\/haematol.2021.279512","article-title":"Treatment of chemotherapy-induced thrombocytopenia in patients with non-hematologic malignancies","volume":"107","author":"Kuter","year":"2022","journal-title":"Haematologica"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/0959-8049(95)00145-9","article-title":"Protection of normal tissues from the cytotoxic effects of chemotherapy and radiation by amifostine (WR-2721): Preclinical aspects","volume":"31","author":"Peters","year":"1995","journal-title":"Eur. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Esp\u00edrito Santo, S.G., Monte, M.G., Polegato, B.F., Barbisan, L.F., and Romualdo, G.R. (2023). Protective effects of omega-3 supplementation against doxorubicin-induced deleterious effects on the liver and kidneys of rats. Molecules, 28.","DOI":"10.3390\/molecules28073004"},{"key":"ref_54","first-page":"293","article-title":"Resveratrol protects against acute chemotherapy toxicity induced by doxorubucin in rat erythrocyte and plasma","volume":"63","author":"Hamlaoui","year":"2012","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1002\/1097-0142(19931201)72:11+<3495::AID-CNCR2820721617>3.0.CO;2-B","article-title":"Amifostine-mediated protection of normal bone marrow from cytotoxic chemotherapy","volume":"1","author":"Capizzi","year":"1993","journal-title":"Cancer"},{"key":"ref_56","first-page":"1035","article-title":"The potential of amifostine: From cytoprotectant to therapeutic agent","volume":"84","author":"Santini","year":"1999","journal-title":"Haematologica"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6604","DOI":"10.1038\/s41598-025-91133-6","article-title":"Mitigating doxorubicin-induced hepatotoxicity in male rats: The role of aerobic interval training and curcumin supplementation in reducing oxidative stress, endoplasmic reticulum stress and apoptosis","volume":"15","author":"Zobeydi","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Manful, C.F., Fordjour, E., Subramaniam, D., Sey, A.A., Abbey, L., and Thomas, R. (2025). Antioxidants and reactive oxygen species: Shaping human health and disease outcomes. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157520"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27203","DOI":"10.1038\/s41598-025-09675-8","article-title":"Aegeline improves doxorubicin-induced liver toxicity by modulating oxidative stress and Bax\/Bcl2\/caspase\/NF-\u03baB signalling","volume":"15","author":"Alsahli","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.jiac.2018.03.010","article-title":"Targeting the proinflammatory cytokines, oxidative stress, apoptosis and TGF-\u03b21\/STAT-3 signalling by irbesartan to ameliorate doxorubicin-induced hepatotoxicity","volume":"24","author":"Kabel","year":"2018","journal-title":"J. Infect. Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Pistone, A., Matera, I., Abruzzese, V., Castiglione Morelli, M.A., Rosa, M., and Ostuni, A. (2025). Enhancing Doxorubicin Efficacy in Hepatocellular Carcinoma: The Multi-Target Role of Muscari comosum Extract. Appl. Sci., 15.","DOI":"10.3390\/app15126509"},{"key":"ref_62","first-page":"347","article-title":"Doxorubicin-induced hepatotoxicity, apoptosis and renal dysfunction: Role of hesperidin in potentiation or attenuation in male Wistar rats","volume":"12","author":"Akwari","year":"2025","journal-title":"Br. J. Health Med. Res."},{"key":"ref_63","first-page":"500","article-title":"Application of comet assay to assess the protective effect of amifostine on doxorubicin-induced DNA damage in human hepatoma cells","volume":"6","author":"Shokrzadeh","year":"2018","journal-title":"EC Pharmacol. Toxicol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1016\/j.sjbs.2020.07.011","article-title":"Doxorubicin-induced alterations in kidney functioning, oxidative stress, DNA damage, and renal tissue morphology; Improvement by Acacia hydaspica tannin-rich ethyl acetate fraction","volume":"27","author":"Afsar","year":"2020","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.toxrep.2023.11.005","article-title":"Nephroprotective effects of diminazene on doxorubicin-induced acute kidney injury in rats","volume":"11","author":"Suleimani","year":"2023","journal-title":"Toxicol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Arunachalam, S., Nagoor Meeran, M.F., Azimullah, S., Jha, N.K., Saraswathiamma, D., Subramanya, S., Albawardi, A., and Ojha, S. (2022). \u03b1-Bisabolol attenuates doxorubicin-induced renal toxicity by modulating nf-\u03bab\/MAPK signalling and caspase-dependent apoptosis in rats. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810528"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"130082","DOI":"10.1016\/j.jhazmat.2022.130082","article-title":"Effects of thiacloprid exposure on microbiota-gut-liver axis: Multiomics mechanistic analysis in Japanese quails","volume":"15","author":"Han","year":"2023","journal-title":"J. Hazard. Mater."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Soltani Hekmat, A., Chenari, A., Alipanah, H., and Javanmardi, K. (2021). Protective effect of alamandine on doxorubicin-induced nephrotoxicity in rats. BMC Pharmacol. Toxicol., 29.","DOI":"10.21203\/rs.3.rs-143651\/v1"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Arozal, W., Eziefule, O.M., Wanandi, S.I., Louisa, M., Dewi, S., Nafrialdi, S.N.C., and Makambwa, E. (2025). Doxorubicin-induced nephrotoxicity: The protective role of a standardised ethanolic extract of Andrographis paniculata leaves. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1585965"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4103\/0253-7613.62401","article-title":"Analgesic and anti-inflammatory activity of amifostine, DRDE-07, and their analogs, in mice","volume":"42","author":"Bhutia","year":"2010","journal-title":"Indian J. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11125","DOI":"10.1158\/0008-5472.CAN-06-3174","article-title":"Tumor necrosis factor-alpha increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: A potential mechanism for inflammation-induced carcinogenesis","volume":"66","author":"Babbar","year":"2006","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s002800050026","article-title":"In vitro antioxidant properties of amifostine (WR-2721, Ethyol)","volume":"45","author":"Marzatico","year":"2000","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1183\/09031936.00014808","article-title":"Amifostine reduces lung vascular permeability via suppression of inflammatory signalling","volume":"33","author":"Fu","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00210-018-1514-4","article-title":"Protective effects of amifostine, curcumin, and melatonin against cisplatin-induced acute kidney injury","volume":"391","author":"Mercantepe","year":"2018","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.aquatox.2017.03.014","article-title":"Acute toxication of deltamethrin results in activation of iNOS, 8-OHdG and up-regulation of caspase 3, iNOS gene expression in common carp (Cyprinus carpio L.)","volume":"187","author":"Arslan","year":"2017","journal-title":"Aquat. Toxicol."},{"key":"ref_76","first-page":"129","article-title":"The link between deacetylation and hepatotoxicity induced by exposure to hexavalent chromium","volume":"8","author":"Yang","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_77","first-page":"313","article-title":"Biomarkers of apoptosis: Release of cytochrome c, activation of caspase-3, induction of 8-hydroxy-2\u2019-deoxyguanosine, increased 3-nitrotyrosine, and alteration of the p53 gene","volume":"4","year":"2001","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Gad, N., Shabana, S., Amer, M., Azza, I.O., and El-Missiry, M.A. (2025). Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect. BMC Pharmacol. Toxicol., 26.","DOI":"10.1186\/s40360-025-00947-7"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1080\/13813455.2017.1422766","article-title":"Chemoprotective effects of curcumin on doxorubicin-induced nephrotoxicity in Wistar rats: By modulating inflammatory cytokines, apoptosis, oxidative stress and oxidative DNA damage","volume":"124","author":"Benzer","year":"2018","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_80","first-page":"3404","article-title":"Protective effects of amifostine, curcumin and caffeic acid phenethyl ester against cisplatin-induced testis tissue damage in rats","volume":"15","author":"Mercantepe","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4130824","DOI":"10.1155\/2017\/4130824","article-title":"Amifostine pretreatment attenuates myocardial ischemia\/reperfusion injury by inhibiting apoptosis and oxidative stress","volume":"2017","author":"Wu","year":"2017","journal-title":"Oxid. Med. Cell Longev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6419\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:40:51Z","timestamp":1784540451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,19]]},"references-count":81,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146419"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146419","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,19]]}}}