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Thymoquinone (TMQ), the main bioactive component of <jats:italic>Nigella sativa<\/jats:italic>, has antioxidant and protective effects against toxicity. In this study, we investigated the protective effect of thymoquinone against cardiotoxicity caused by 5\u2010FU in vitro and in vivo models. H9C2 cells were exposed to 5\u2010FU and TMQ, and cell viability was evaluated in their presence. Also, 25 male Wistar rats were divided into five control groups, 5\u2010FU, 2.5, and 5\u2009mg TMQ in nanoemulsion form (NTMQ)\u2009+\u20095\u2010FU and 5\u2009mg NTMQ. Cardiotoxicity was assessed through electrocardiography, cardiac enzymes, oxidative stress markers, and histopathology. 5\u2010FU induced cytotoxicity in H9c2 cells, which improved dose\u2010dependently with NTMQ cotreatment. 5\u2010FU caused body weight loss, ECG changes (increased ST segment, prolonged QRS, and QTc), increased cardiac enzymes (aspartate aminotransferase [AST], creatine kinase\u2010myocardial band [CK\u2010MB], and lactate dehydrogenase [LDH]), oxidative stress (increased malondialdehyde, myeloperoxidase, nitric acid; decreased glutathione peroxidase enzyme activity), and histological damage such as necrosis, hyperemia, and tissue hyalinization in rats. NTMQ ameliorated these 5\u2010FU\u2010induced effects. Higher NTMQ dose showed greater protective effects. Thus, the results of our study indicate that NTMQ protects against 5\u2010FU cardiotoxicity likely through antioxidant mechanisms. TMQ warrants further research as an adjuvant to alleviate 5\u2010FU chemotherapy side effects.<\/jats:p>","DOI":"10.1002\/ddr.22171","type":"journal-article","created":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T02:13:05Z","timestamp":1709950385000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Protective effect of thymoquinone nanoemulsion in reducing the cardiotoxic effect of 5\u2010fluorouracil in rats"],"prefix":"10.1002","volume":"85","author":[{"given":"Bardia","family":"Karim","sequence":"first","affiliation":[{"name":"Student Research Committee Babol University of Medical Sciences  Babol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motahare","family":"Arabameri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ayatollah Amoli Branch Islamic Azad University  Amol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Alimoradi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ayatollah Amoli Branch Islamic Azad University  Amol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razieh","family":"Mansoori","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center, Health Research Institute Babol University of Medical Sciences  Babol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0100-978X","authenticated-orcid":false,"given":"Ali A.","family":"Moghadamnia","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center, Health Research Institute Babol University of Medical Sciences  Babol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8068-5745","authenticated-orcid":false,"given":"Sohrab","family":"Kazemi","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology Research Center, Health Research Institute Babol University of Medical Sciences  Babol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed M.","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, Babol\u2010Branch Islamic Azad University  Babol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0102-865020160040000008"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.repc.2020.12.015"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-12-86"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.5897\/JPAP2013.0083"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1483041"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.01.043"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-12735-y"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12594-8"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2018.1454459"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2004.12.014"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.06.015"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.07.018"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-015-0391-0"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.5.466"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-014-3137-2"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-021-02087-1"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjtm.2017.08.020"},{"key":"e_1_2_11_19_1","first-page":"1","volume-title":"Encyclopedia of Polymer Science and Technology","author":"Guarino V.","year":"2002"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2017.03.088"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22618"},{"key":"e_1_2_11_22_1","first-page":"165","article-title":"The antioxidant power and level of lipid peroxidation products in the sera of apparently healthy adult males","volume":"31","author":"Katalini\u0107 V.","year":"2007","journal-title":"Collegium Antropologicum"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000331645"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-007-0250-9"},{"key":"e_1_2_11_25_1","first-page":"63","article-title":"5\u2010fluorouracil induced cardiotoxicity in albino rats","volume":"27","author":"Kumar S.","year":"1995","journal-title":"Materia Medica Polona. 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