{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:37:15Z","timestamp":1792255035280,"version":"4.4.0"},"reference-count":72,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cardiotoxicity is one of the most devastating complications of cancer treatment by methotrexate (MTX). The present study aimed to investigate the potential anti\u2010cardiotoxic efficacy of taurine (Tau) and enzymatically modified isoquercitrin (EMIQ) alone or combined against MTX\u2010induced cardiotoxicity in adult male rats. A total of 36 rats were randomly divided into six groups (six animals each): control, MTX (a single i.p. dose of 20\u2009mg\/kg), EMIQ\u2009+\u2009MTX (26\u2009mg\/kg of EMIQ, p.o. for 16\u2009days), Tau\u2009+\u2009MTX (500\u2009mg\/kg of Tau, p.o. for 16\u2009days), EMIQ\u2009+\u2009Tau\u2009+\u2009MTX at the same previous doses, and (EMIQ\u2009+\u2009Tau)<jats:sub>\u00bd<\/jats:sub>\u00a0+\u2009MTX. MTX reduced the percentage of body weight change, the expression of dihydrofolate reductase (<jats:italic>DHFR<\/jats:italic>) and folypolyglutamyl synthetase (<jats:italic>FPGS<\/jats:italic>), the cleaved tumor necrosis factor alpha (TNF\u2010\u03b1) level in the cardiac tissue, and the elevated serum TNF\u2010\u03b1 level. MTX extensively deteriorated the electrocardiography (ECG), inducing tachycardia with shortening of the time intervals between successive heartbeats (R\u2010R interval), associated with elongation of ventricular depolarization (QRS interval), and the corrected total time for ventricular de\u2010 and repolarization (QTc) duration. Treatment with MTX resulted in a significant reduction in atrial depolarization (P amplitude) and rapid repolarization (T amplitude) and a significant elevation in plateau phase (ST height). MTX treatment resulted in swelling of cardiomyocytes with extensive vacuolization of sarcoplasm with numerous variably sized vacuoles in addition to apoptotic cells. Tau and EMIQ protected against MTX\u2010induced deteriorations in the conductivity and rhythmicity of the heart through antioxidative, anti\u2010inflammatory, and antiapoptotic activities. Treatment with tau and EMIQ combined at high or low doses offered superior protection to the heart than using each agent alone.<\/jats:p>","DOI":"10.1002\/jat.4682","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:13Z","timestamp":1723507213000},"page":"1924-1935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Taurine and enzymatically modified isoquercitrin protected against methotrexate\u2010induced deteriorations in the conductivity and rhythmicity of the heart in rats: Antioxidant, anti\u2010inflammatory, and histological architecture approach"],"prefix":"10.1002","volume":"44","author":[{"given":"Marwa M.","family":"Mahmoud","sequence":"first","affiliation":[{"name":"Department of Zoology, Faculty of Science Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seham A.","family":"El\u2010Batran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical Division National Research Centre  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical Division National Research Centre  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3622-1417","authenticated-orcid":false,"given":"Wael M.","family":"El\u2010Sayed","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Science Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14100970"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/19390211.2016.1267059"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-021-09644-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15060674"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2015-0138"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.14670\/HH-29.45"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8641026"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050312120965752"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/c8fo00131f"},{"key":"e_1_2_8_11_1","first-page":"295","volume-title":"Engineered nanoparticles","author":"Ashok K.","year":"2016"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/09603271211047924"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199447010-00003"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs351"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology10070586"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12198"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/cgt.2013.48"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094457"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1301"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.01.008"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5926381"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2018.07.005"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553002.2020.1828656"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2011.05.100"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4103\/0973-1296.176106"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3177\/jnsv.53.68"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imr.2018.05.001"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.29518"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-023-03884-w"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2018.0226"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/anec.12730"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21074"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0303060"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.665031"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12970-017-0190-y"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S445412"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200010)43:10<2169::AID-ANR4>3.0.CO;2-#"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568010054526359"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1139\/y05-009"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.22038\/IJBMS.2024.74161.16120"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/futurepharmacol3040049"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.070036297"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.2459\/JCM.0000000000000376"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_202110_26879"},{"issue":"03","key":"e_1_2_8_45_1","first-page":"479","article-title":"Cardioprotective activity of polyphenolic extract of tubers of Cyperus\u2009rotundus and taurine against isoproterenol\u2010induced myocardial infraction in rats: Troponin\u2010I and histological findings","volume":"10","author":"Majid A.","year":"2018","journal-title":"Journal of Global Pharma Technology"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.32.2034"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2004.03.040"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2017.03.007"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12970-019-0303-x"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232314784"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.111.137877"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12092847"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-019-09535-8"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14060510"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27082564"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-013-9230-2"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8090-6-31"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-016-2767-1"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0242175"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13256-022-03644-9"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901721R"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-023-01525-1"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.582449"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12726"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306565"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.049478"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.06.002"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-024-1079-2_65"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.4103\/MMJ.MMJ_183_17"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-019-0260-8"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2013.1264"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-017-1351-9"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.06.029"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4682","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T08:35:20Z","timestamp":1760517320000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,12]]},"references-count":72,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/jat.4682"],"URL":"https:\/\/doi.org\/10.1002\/jat.4682","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,12]]},"assertion":[{"value":"2024-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}