{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:30:33Z","timestamp":1790022633440,"version":"4.0.1"},"reference-count":60,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>For many years, 5-fluorouracil (5-FU) has been utilized as a chemotherapeutic treatment for a variety of malignancies. Unfortunately, 5-FU causes cardiotoxicity, which restricts its clinical use. Nifuroxazide (NFX) is a STAT-3 inhibitor with antioxidant and anti-inflammatory effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cardiotoxicity was induced by 5-FU (30\u00a0mg\/kg) once daily for 5 days. NFX was administered in two doses, 25 and 50\u00a0mg.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to 5-FU-control rats, NFX significantly attenuates cardiotoxicity induced by 5-FU, as indicated by decreasing creatine kinase (CK)-MB, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) serum levels. Histopathological examinations confirmed the protective effects of NFX against histological abrasions induced by 5-FU. NFX attenuated the oxidative damage induced by 5-FU mediated by peroxisome proliferator-activated receptor gamma (PPAR-\u03b3) signal activation. Moreover, NFX mitigated 5-FU-induced inflammation by suppressing nucleotide-binding domain, leucine-rich repeat-containing protein 3\/signal transducer and activator of transcription 3 (NLRP3\/STAT3) signal activation. Notably, these protective effects are dose-dependent. Additionally, NFX mitigated 5-FU-induced apoptosis by downregulating Bax, while upregulating Bcl-2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, NFX attenuated 5-FU-induced cardiac intoxication by regulating NLRP3\/STAT-3, PPAR-\u03b3, and Bax\/Bcl-2 signals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09603271251371245","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T09:03:35Z","timestamp":1756112615000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Nifuroxazide attenuated 5-fluorouracil-induced cardiac intoxication by regulating NLRP3\/STAT-3, PPAR-\u03b3, and apoptosis signals"],"prefix":"10.1177","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2981-2622","authenticated-orcid":false,"given":"Nouf S.","family":"Al-Abbas","sequence":"first","affiliation":[{"name":"Department of Biology, Jamoum University College, Umm Al-Qura University, Makkah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehad A.","family":"Shaer","sequence":"additional","affiliation":[{"name":"Department of Biology, Jamoum University College, Umm Al-Qura University, Makkah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0348-1"},{"issue":"2","key":"e_1_3_8_3_2","first-page":"75","article-title":"Chemotherapy and cardiotoxicity","volume":"9","author":"Broder H","year":"2008","unstructured":"Broder H, Gottlieb RA, Lepor NE. Chemotherapy and cardiotoxicity. Rev Cardiovasc Med 2008; 9(2): 75\u201383.","journal-title":"Rev Cardiovasc Med"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1074"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198916040-00002"},{"issue":"1","key":"e_1_3_8_6_2","first-page":"1","article-title":"Synergistic effect of cold atmospheric plasma and drug loaded core-shell nanoparticles on inhibiting","volume":"6","author":"Zhu W","year":"2016","unstructured":"Zhu W, Lee S-J, Castro NJ, et al. Synergistic effect of cold atmospheric plasma and drug loaded core-shell nanoparticles on inhibiting. Breast Cancer Cell Growth 2016; 6(1): 1\u201311.","journal-title":"Breast Cancer Cell Growth"},{"issue":"4","key":"e_1_3_8_7_2","first-page":"531","article-title":"Bolus 5-fluorouracil as an alternative in patients with cardiotoxicity associated with infusion 5-fluorouracil and capecitabine: a case series","volume":"27","author":"Saif MW","year":"2013","unstructured":"Saif MW, Garcon MC, Rodriguez G, et al. Bolus 5-fluorouracil as an alternative in patients with cardiotoxicity associated with infusion 5-fluorouracil and capecitabine: a case series. In Vivo 2013; 27(4): 531\u2013534.","journal-title":"In Vivo"},{"key":"e_1_3_8_8_2","first-page":"175883591878014","article-title":"5-fluorouracil and cardiotoxicity: a review","volume":"10","author":"Sara JD","year":"2018","unstructured":"Sara JD, Kaur J, Khodadadi R, et al. 5-fluorouracil and cardiotoxicity: a review. A Review 2018; 10: 1758835918780140.","journal-title":"A Review"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-021-07214-x"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00352"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.02.007"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6404638"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-019-00724-4"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175776"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-12-129718"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2018.09.005"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.63"},{"issue":"1","key":"e_1_3_8_18_2","first-page":"1","article-title":"Nifuroxazide exerts potent anti-tumor and anti-metastasis activity in melanoma","volume":"6","author":"Zhu Y","year":"2016","unstructured":"Zhu Y, Ye T, Yu X, et al. Nifuroxazide exerts potent anti-tumor and anti-metastasis activity in melanoma. Sci Rep 2016; 6(1): 1\u201313.","journal-title":"Sci Rep"},{"issue":"1","key":"e_1_3_8_19_2","first-page":"46","article-title":"Potential role of signal transducer and activator of transcription (STAT) 3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma","volume":"1835","author":"Subramaniam A","year":"2013","unstructured":"Subramaniam A, Shanmugam MK, Perumal E, et al. Potential role of signal transducer and activator of transcription (STAT) 3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochim Biophys Acta 2013; 1835(1): 46\u201360.","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_8_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119433"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5673272"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-020-11416-5"},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(78)90342-1"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(85)90216-7"},{"key":"e_1_3_8_26_2","unstructured":"Montgomery H Dymock JFJA. Determination of nitrite in water Royal Soc Chemistry Thomas Graham House Science Park Milton Rd CAMBRIDGE 1961 p. 414."},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(84)90202-6"},{"key":"e_1_3_8_28_2","first-page":"53","volume-title":"Theory and practice of histological techniques","author":"Bancroft JD","year":"2008","unstructured":"Bancroft JD, Gamble M. Theory and practice of histological techniques. Elsevier Health Sciences, 2008, pp. 53\u201374."},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600967"},{"key":"e_1_3_8_31_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.00.5686"},{"key":"e_1_3_8_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2021.153042"},{"issue":"1","key":"e_1_3_8_33_2","first-page":"1","article-title":"The possible cardio-protective effects of ethanolic artichoke extract against 5-fluorouracil induced cardiac toxicity in rats","volume":"25","author":"Numan IT","year":"2016","unstructured":"Numan IT, Hamad MN, Fadhil AA, et al. The possible cardio-protective effects of ethanolic artichoke extract against 5-fluorouracil induced cardiac toxicity in rats. Iraqi J Pharm Sci 2016; 25(1): 1\u20135.","journal-title":"Iraqi J Pharm Sci"},{"key":"e_1_3_8_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117907"},{"key":"e_1_3_8_35_2","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2014.942809"},{"key":"e_1_3_8_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2004.12.014"},{"issue":"3","key":"e_1_3_8_37_2","first-page":"395","article-title":"Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions","volume":"107","author":"Fantone JC","year":"1982","unstructured":"Fantone JC, Ward PA. Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol 1982; 107(3): 395\u2013418.","journal-title":"Am J Pathol"},{"key":"e_1_3_8_38_2","doi-asserted-by":"publisher","DOI":"10.1177\/106002809402800314"},{"key":"e_1_3_8_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c06475"},{"key":"e_1_3_8_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.7.596"},{"issue":"11","key":"e_1_3_8_41_2","first-page":"457","article-title":"Peroxisome proliferator-activated receptor gamma: a key regulator of adipogenesis and systemic insulin sensitivity","volume":"2","author":"Spiegelman BM","year":"1997","unstructured":"Spiegelman BM. Peroxisome proliferator-activated receptor gamma: a key regulator of adipogenesis and systemic insulin sensitivity. Eur J Med Res 1997; 2(11): 457\u2013464.","journal-title":"Eur J Med Res"},{"key":"e_1_3_8_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00569-6"},{"key":"e_1_3_8_43_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.77.061307.091829"},{"key":"e_1_3_8_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002577200"},{"key":"e_1_3_8_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh657"},{"key":"e_1_3_8_46_2","doi-asserted-by":"publisher","DOI":"10.1177\/0192623307313010"},{"key":"e_1_3_8_47_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986709788682155"},{"key":"e_1_3_8_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.24.1879"},{"key":"e_1_3_8_49_2","doi-asserted-by":"publisher","DOI":"10.1080\/13510002.1997.11747120"},{"key":"e_1_3_8_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjbas.2016.05.001"},{"issue":"7","key":"e_1_3_8_51_2","first-page":"1139","article-title":"Serum levels of NFkappaB and pro-inflammatory cytokines following administration of mucotoxic drugs","volume":"7","author":"Logan RM","year":"2008","unstructured":"Logan RM, Stringer AM, Bowen JM, et al. Serum levels of NFkappaB and pro-inflammatory cytokines following administration of mucotoxic drugs. Drugs 2008; 7(7): 1139\u20131145.","journal-title":"Drugs"},{"key":"e_1_3_8_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.97"},{"key":"e_1_3_8_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119754"},{"key":"e_1_3_8_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22889"},{"key":"e_1_3_8_55_2","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2020.1811307"},{"key":"e_1_3_8_56_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-017-0553-x"},{"key":"e_1_3_8_57_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.46873"},{"key":"e_1_3_8_58_2","doi-asserted-by":"publisher","DOI":"10.15430\/JCP.2017.22.3.189"},{"key":"e_1_3_8_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112599"},{"key":"e_1_3_8_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-017-3147-1"},{"key":"e_1_3_8_61_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23169082"}],"container-title":["Human &amp; Experimental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09603271251371245","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/09603271251371245","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09603271251371245","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:49:28Z","timestamp":1777448968000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/09603271251371245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":60,"alternative-id":["10.1177\/09603271251371245"],"URL":"https:\/\/doi.org\/10.1177\/09603271251371245","relation":{},"ISSN":["0960-3271","1477-0903"],"issn-type":[{"value":"0960-3271","type":"print"},{"value":"1477-0903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"article-number":"09603271251371245"}}