{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:02:31Z","timestamp":1791910951437,"version":"4.3.4"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Chemico-Biological Interactions"],"published-print":{"date-parts":[[2016,3]]},"DOI":"10.1016\/j.cbi.2016.01.014","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T16:01:58Z","timestamp":1453478518000},"page":"39-48","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":72,"special_numbering":"C","title":["Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptic pathways"],"prefix":"10.1016","volume":"247","author":[{"given":"Nehal M.","family":"Elsherbiny","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed F.","family":"Salama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Said","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Sherbiny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed M.H.","family":"Al-Gayyar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cbi.2016.01.014_bib1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s13105-014-0339-y","article-title":"Protective effect of resveratrol against doxorubicin-induced cardiac toxicity and fibrosis in male experimental rats","volume":"70","author":"Arafa","year":"2014","journal-title":"J.\u00a0Physiol. Biochem."},{"key":"10.1016\/j.cbi.2016.01.014_bib2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.cbi.2014.09.015","article-title":"Thymoquinone attenuates Doxorubicin-induced nephrotoxicity in rats: Role of Nrf2 and NOX4","volume":"223","author":"Elsherbiny","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.cbi.2016.01.014_bib3","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/748524","article-title":"Nrf2 deficiency exaggerates doxorubicin-induced cardiotoxicity and cardiac dysfunction","author":"Li","year":"2014","journal-title":"Oxid. Med. Cell Longev."},{"key":"10.1016\/j.cbi.2016.01.014_bib4","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s12012-014-9249-z","article-title":"Morphine enhances doxorubicin-induced cardiotoxicity in the rat","volume":"14","author":"Hole","year":"2014","journal-title":"Cardiovasc Toxicol."},{"key":"10.1016\/j.cbi.2016.01.014_bib5","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1161\/CIRCULATIONAHA.109.895771","article-title":"Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell pool and is rescued by restoration of progenitor cell function","volume":"121","author":"De Angelis","year":"2010","journal-title":"Circulation"},{"key":"10.1016\/j.cbi.2016.01.014_bib6","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.niox.2012.03.006","article-title":"Dietary inorganic nitrate alleviates doxorubicin cardiotoxicity: mechanisms and implications","volume":"26","author":"Xi","year":"2012","journal-title":"Nitric Oxide"},{"key":"10.1016\/j.cbi.2016.01.014_bib7","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1023\/A:1015976430790","article-title":"Doxorubicin-induced apoptosis: implications in cardiotoxicity","volume":"234\u2013235","author":"[Kalyanaraman","year":"2002","journal-title":"Mol. Cell Biochem."},{"key":"10.1016\/j.cbi.2016.01.014_bib8","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.bbrc.2008.06.067","article-title":"Vincristine attenuates doxorubicin cardiotoxicity","volume":"373","author":"Chatterjee","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.cbi.2016.01.014_bib9","article-title":"Diazoxide protects against doxorubicin-induced cardiotoxicity in the rat","volume":"1528","author":"Hole","year":"2014","journal-title":"BMC Pharmacol. Toxicol."},{"key":"10.1016\/j.cbi.2016.01.014_bib10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10571-009-9441-z","article-title":"Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicity in PC12 cells","volume":"30","author":"Mousavi","year":"2010","journal-title":"Cell Mol. Neurobiol."},{"key":"10.1016\/j.cbi.2016.01.014_bib11","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1016\/j.fct.2008.08.018","article-title":"Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines","volume":"46","author":"Tavakkol-Afshari","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.cbi.2016.01.014_bib12","first-page":"10744","article-title":"Crocin prevents retinal ischaemia\/reperfusion injury-induced apoptosis in retinal ganglion cells through the PI3K\/AKT signalling pathway","author":"Qi","year":"2013","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.cbi.2016.01.014_bib13","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.cbi.2013.03.010","article-title":"Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure","volume":"203","author":"Razavi","year":"2013","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.cbi.2016.01.014_bib14","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11010-012-1476-7","article-title":"Crocin, a dietary additive protects platelets from oxidative stress-induced apoptosis and inhibits platelet aggregation","volume":"373","author":"Thushara","year":"2013","journal-title":"Mol. Cell Biochem."},{"key":"10.1016\/j.cbi.2016.01.014_bib15","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s12272-013-0128-0","article-title":"Anti-inflammatory activities of crocetin derivatives from processed Gardenia jasminoides","volume":"36","author":"Hong","year":"2013","journal-title":"Arch. Pharm. Res."},{"key":"10.1016\/j.cbi.2016.01.014_bib16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00011-012-0546-3","article-title":"Anti-arthritic effects of crocin in interleukin-1beta-treated articular chondrocytes and cartilage in a rabbit osteoarthritic model","volume":"62","author":"Ding","year":"2013","journal-title":"Inflamm. Res."},{"key":"10.1016\/j.cbi.2016.01.014_bib17","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/135048","article-title":"Antitumor effects of saffron-derived carotenoids in prostate cancer cell models","author":"Festuccia","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"10.1016\/j.cbi.2016.01.014_bib18","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.lfs.2005.02.006","article-title":"Effect of crocin on experimental atherosclerosis in quails and its mechanisms","volume":"77","author":"He","year":"2005","journal-title":"Life Sci."},{"key":"10.1016\/j.cbi.2016.01.014_bib19","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s12010-009-8740-7","article-title":"Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats","volume":"162","author":"Asdaq","year":"2010","journal-title":"Appl. Biochem. Biotechnol."},{"key":"10.1016\/j.cbi.2016.01.014_bib20","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/ptr.3566","article-title":"Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats","volume":"26","author":"Hosseinzadeh","year":"2012","journal-title":"Phytother. Res."},{"key":"10.1016\/j.cbi.2016.01.014_bib21","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1055\/s-0033-1360383","article-title":"Protective effects of crocin on hemodynamic parameters and infarct size in comparison with vitamin E after ischemia reperfusion in isolated rat hearts","volume":"80","author":"Dianat","year":"2014","journal-title":"Planta Med."},{"issue":"4","key":"10.1016\/j.cbi.2016.01.014_bib22","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1093\/ajcp\/58.5.376","article-title":"Rapid colorimetric determination of calcium in biologic fluids with methylthymol blue","volume":"58","author":"Gindler","year":"1972","journal-title":"Am. J. Clin. Pathol."},{"key":"10.1016\/j.cbi.2016.01.014_bib23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0009-8981(78)90081-5","article-title":"Serum lipid peroxide in cerebrovascular disorder determined by a new colorimetric method","volume":"90","author":"Satoh","year":"1978","journal-title":"Clin. Chem. Acta"},{"issue":"2","key":"10.1016\/j.cbi.2016.01.014_bib24","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0006-291X(72)80218-3","article-title":"The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen","volume":"46","author":"Nishikimi","year":"1972","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.cbi.2016.01.014_bib25","first-page":"1192","article-title":"Protective Effect of Solanum Torvum on Doxorubicin-Induced Cardiactoxicity in Rats","volume":"2","author":"Kamble","year":"2009","journal-title":"Pharmacol. online"},{"key":"10.1016\/j.cbi.2016.01.014_bib26","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.bbamcr.2011.03.002","article-title":"Changes in mitochondrial redox state, membrane potential and calcium precede mitochondrial dysfunction in doxorubicin-induced cell death","volume":"1813","author":"Kuznetsov","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.cbi.2016.01.014_bib27","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1631\/jzus.2003.0114","article-title":"Study on the effects of doxorubicin on expression of genes encoding myocardiac sarcoplasmic reticulum Ca2+ transport myocardiac protection in rabbits","volume":"4","author":"Huang","year":"2003","journal-title":"J.\u00a0Zhejiang Univ. Sci."},{"key":"10.1016\/j.cbi.2016.01.014_bib28","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1253\/jcj.62.505","article-title":"Doxorubicin cardiotoxicity. Diastolic cardiac Ca2+ handing in isolated cardiac myocytes","volume":"62","author":"Maeda","year":"1998","journal-title":"Jpn. Circ."},{"key":"10.1016\/j.cbi.2016.01.014_bib29","first-page":"771","article-title":"Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin","volume":"61","author":"Zhou","year":"2001","journal-title":"Cancer Res."},{"key":"10.1016\/j.cbi.2016.01.014_bib30","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1161\/01.RES.86.1.8","article-title":"Mechanism of doxorubicin \u2013 induced inhibition of sarcoplasmic reticulum Ca2+ ATPase gene transcription","volume":"86","author":"Arai","year":"2000","journal-title":"Circ. Res."},{"issue":"17","key":"10.1016\/j.cbi.2016.01.014_bib31","first-page":"4049","article-title":"Cardioprotective effects of Curcuma longa L. extracts against doxorubicin-induced cardiotoxicity in rats","volume":"5","author":"El-Sayed","year":"2011","journal-title":"J.\u00a0Med. Plants Res."},{"issue":"5","key":"10.1016\/j.cbi.2016.01.014_bib32","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/emm.2006.63","article-title":"Doxorubicin \u2013 induced reactive oxygen species generation and intracellular \u2013 Ca2+ increase are reciprocally modulated in rat cardiomyocytes","volume":"38","author":"Kim","year":"2006","journal-title":"Exp. Mol. Med."},{"issue":"5","key":"10.1016\/j.cbi.2016.01.014_bib33","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1248\/bpb.31.809","article-title":"Fatty acids ameliorate doxorubicin\u2013 induced intracellular Ca+2 increase and apoptosis in rat cardiomyocytes","volume":"31","author":"Park","year":"2008","journal-title":"Biol. Pharma Bull."},{"key":"10.1016\/j.cbi.2016.01.014_bib34","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.yjmcc.2012.03.006","article-title":"Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies","volume":"52","author":"Octavia","year":"2012","journal-title":"J.\u00a0Mol. Cell Cardiol."},{"key":"10.1016\/j.cbi.2016.01.014_bib35","doi-asserted-by":"crossref","first-page":"644","DOI":"10.3892\/ijmm.2013.1246","article-title":"Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibition of the p38 MAPK pathway in H9c2 cells","volume":"31","author":"Guo","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.cbi.2016.01.014_bib36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1254\/jphs.FP0050980","article-title":"Doxorubicin induces apoptosis by activation of caspase-3 in cultured cardiomyocytes in\u00a0vitro and rat cardiac ventricles in\u00a0vivo","volume":"101","author":"Ueno","year":"2006","journal-title":"J.\u00a0Pharmacol. Sci."},{"key":"10.1016\/j.cbi.2016.01.014_bib37","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1742-7843.2007.00001.x","article-title":"Increased expression ratio of Bcl-2\/Bax is associated with crocin-mediated apoptosis in bovine aortic endothelial cells","volume":"100","author":"Xu","year":"2007","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"10.1016\/j.cbi.2016.01.014_bib38","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/728709","article-title":"Crocin suppresses LPS-stimulated expression of inducible nitric oxide synthase by upregulation of heme oxygenase-1 via calcium\/calmodulin-dependent protein kinase 4","author":"Kim","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.cbi.2016.01.014_bib39","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.phymed.2012.12.019","article-title":"Protective effects of oral crocin against intracerebroventricular streptozotocin-induced spatial memory deficit and oxidative stress in rats","volume":"20","author":"Naghizadeh","year":"2013","journal-title":"Phytomedicine"},{"key":"10.1016\/j.cbi.2016.01.014_bib40","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s10238-011-0165-2","article-title":"Catechin protects against oxidative stress and inflammatory-mediated cardiotoxicity in adriamycin-treated rats","volume":"12","author":"Abd El-Aziz","year":"2012","journal-title":"Clin. Exp. Med."},{"key":"10.1016\/j.cbi.2016.01.014_bib41","doi-asserted-by":"crossref","first-page":"31279","DOI":"10.1371\/journal.pone.0031279","article-title":"Increased expression of integrin-linked kinase improves cardiac function and decreases mortality in dilated cardiomyopathy model of rats","volume":"7","author":"Gu","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.cbi.2016.01.014_bib42","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ejphar.2010.09.003","article-title":"Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells","volume":"648","author":"Nam","year":"2010","journal-title":"Eur. J. Pharmacol."},{"issue":"2012","key":"10.1016\/j.cbi.2016.01.014_bib43","first-page":"820415","article-title":"Dietary Crocin Inhibits Colitis and ColitisAssociated Colorectal Carcinogenesis in Male ICR Mice","volume":"2012","author":"Kawabata","year":"2012","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"10.1016\/j.cbi.2016.01.014_bib44","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1172\/JCI116379","article-title":"Doxorubicin cardiomyopathy is associated with a decrease in calcium release channel of the sarcoplasmic reticulum in a chronic rabbit model","volume":"91","author":"Dodd","year":"1993","journal-title":"J.\u00a0Clin. Investig."},{"key":"10.1016\/j.cbi.2016.01.014_bib45","doi-asserted-by":"crossref","first-page":"15851","DOI":"10.1016\/S0021-9258(18)47666-1","article-title":"The major metabolite of doxorubicin is a potent inhibitor of membrane-associated ion pumps. A correlative study of cardiac muscle with isolated membrane fractions","volume":"262","author":"Boucek","year":"1987","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.cbi.2016.01.014_bib46","first-page":"22","article-title":"Medicinal Uses and Pharmacological Properties of Crocus sativus linn (Saffron)","volume":"3","author":"Bhargava","year":"2011","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"10.1016\/j.cbi.2016.01.014_bib47","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1002\/ptr.3044","article-title":"Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats","volume":"24","author":"Imenshahidi","year":"2010","journal-title":"Phytother. Res."},{"key":"10.1016\/j.cbi.2016.01.014_bib48","first-page":"9","article-title":"Effects of chronic crocin treatment on desoxycorticosterone acetate (doca)-salt hypertensive rats","volume":"17","author":"Imenshahidi","year":"2014","journal-title":"Iran. J. Basic Med. Sci."},{"key":"10.1016\/j.cbi.2016.01.014_bib49","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1016\/j.fct.2010.07.010","article-title":"Sub-acute effects of diazinon on biochemical indices and specific biomarkers in rats: protective effects of crocin and safranal","volume":"48","author":"Hariri","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.cbi.2016.01.014_bib50","first-page":"778","article-title":"Effect of crocin on intracellular calcium concentration in cultured bovine aortic smooth muscle cells","volume":"39","author":"He","year":"2004","journal-title":"Yao Xue Xue Bao"},{"issue":"11\u201312","key":"10.1016\/j.cbi.2016.01.014_bib51","doi-asserted-by":"crossref","first-page":"459","DOI":"10.5560\/znc.2014-0124","article-title":"Cardioprotective effect of saffron extracts against acute doxorubicin toxicity in isolated rabbit hearts submitted to ischemia-reperfusion injury","volume":"69","author":"Chahine","year":"2014","journal-title":"Z.\u00a0Naturforsch C J. Biosci."}],"updated-by":[{"DOI":"10.1016\/j.cbi.2016.03.001","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T00:00:00Z","timestamp":1461542400000}}],"container-title":["Chemico-Biological Interactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000927971630014X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000927971630014X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T13:38:20Z","timestamp":1757857100000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S000927971630014X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3]]},"references-count":51,"alternative-id":["S000927971630014X"],"URL":"https:\/\/doi.org\/10.1016\/j.cbi.2016.01.014","relation":{"erratum":[{"id-type":"doi","id":"10.1016\/j.cbi.2016.03.001","asserted-by":"object"}]},"ISSN":["0009-2797"],"issn-type":[{"value":"0009-2797","type":"print"}],"subject":[],"published":{"date-parts":[[2016,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptic pathways","name":"articletitle","label":"Article Title"},{"value":"Chemico-Biological Interactions","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cbi.2016.01.014","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2016 Elsevier Ireland Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}