{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:02:28Z","timestamp":1787374948432,"version":"build-2736575974"},"reference-count":56,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"College of Medicine &amp; Health Sciences, United Arab Emirates University, CMHS","award":["NP-18-29"],"award-info":[{"award-number":["NP-18-29"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Doxorubicin (DOXO) is an effective drug that is used in the treatment of a large number of cancers. Regardless of its important chemotherapeutic characteristics, its usage is restricted because of its serious side effects; the most obvious is cardiotoxicity, which can manifest acutely or years after completion of treatment, leading to left ventricular dysfunction, dilated cardiomyopathy, and heart failure. Galectin 3 (Gal-3) is a beta galactoside binding lectin that has different roles in normal and pathophysiological conditions. Gal-3 was found to be upregulated in animal models, correlating with heart failure, atherosclerosis, and myocardial infarction. Male C57B6\/J and B6.Cg-Lgals3 &lt;tm 1 Poi&gt;\/J Gal-3 knockout (KO) mice were used for a mouse model of acute DOXO-induced cardiotoxicity. Mice were given DOXO or vehicle (normal saline), after which the mice again had free access to food and water. Heart and plasma samples were collected 5 days after DOXO administration and were used for tissue processing, staining, electron microscopy, and enzyme-linked immunosorbent assay (ELISA). There was a significant increase in the heart concentration of Gal-3 in Gal-3 wild type DOXO-treated mice when compared with the sham control. There were significantly higher concentrations of heart cleaved caspase-3, plasma troponin I, plasma lactate dehydrogenase, and plasma creatine kinase in Gal-3 KO DOXO-treated mice than in Gal-3 wild type DOXO-treated mice. Moreover, there were significantly higher heart antioxidant proteins and lower oxidative stress in Gal-3 wild type DOXO-treated mice than in Gal-3 KO DOXO-treated mice. In conclusion, Gal-3 can affect the redox pathways and regulate cell survival and death of the myocardium following acute DOXO injury.<\/jats:p>","DOI":"10.3390\/ijms232012479","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T21:18:02Z","timestamp":1666127882000},"page":"12479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Early Doxorubicin Myocardial Injury: Inflammatory, Oxidative Stress, and Apoptotic Role of Galectin-3"],"prefix":"10.3390","volume":"23","author":[{"given":"Suhail","family":"Al-Salam","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthishwaran","family":"Kandhan","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0646-8504","authenticated-orcid":false,"given":"Manjusha","family":"Sudhadevi","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5867-2833","authenticated-orcid":false,"given":"Javed","family":"Yasin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Tariq","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1542\/peds.2012-0727","article-title":"Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium. Continuous Versus Bolus Infusion of Doxorubicin in Children With ALL: Long-term Cardiac Outcomes","volume":"130","author":"Lipshultz","year":"2012","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1007\/s11886-013-0362-6","article-title":"Cardiac Toxicity of Anticancer Agents","volume":"15","author":"Colombo","year":"2013","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/FJC.0b013e31824cc427","article-title":"Autophagy in the heart: Too much of a good thing?","volume":"60","author":"Wang","year":"2012","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000265166","article-title":"Doxorubicin cardiomyopathy","volume":"115","author":"Chatterjee","year":"2010","journal-title":"Cardiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00005-009-0051-8","article-title":"Cardiomyocyte death in doxorubicin-induced cardiotoxicity","volume":"57","author":"Zhang","year":"2009","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1172\/JCI72931","article-title":"Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation","volume":"124","author":"Ichikawa","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4837","DOI":"10.18632\/oncotarget.13596","article-title":"Astragalus polysaccharide restores autophagic flux and improves cardiomyocyte function in doxorubicin-induced cardiotoxicity","volume":"8","author":"Cao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.bbabio.2013.10.006","article-title":"Functional role of cardiolipin in mitochondrial bioenergetics","volume":"1837","author":"Paradies","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1385\/CT:3:2:89","article-title":"Dexrazoxane (ICRF-187) Protects Cardiac Myocytes Against Doxorubicin by Preventing Damage to Mitochondria","volume":"3","author":"Hasinoff","year":"2003","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0301-4622(90)80012-V","article-title":"Structure of the adriamycin-cardiolipin complex: Role in mitochondrial toxicity","volume":"35","author":"Goormaghtigh","year":"1990","journal-title":"Biophys. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.yjmcc.2009.07.024","article-title":"Chronic doxorubicin cardiotoxicity is mediated by oxidative DNA damage-ATM-p53-apoptosis pathway and attenuated by pitavastatin through the inhibition of Rac1 activity","volume":"47","author":"Yoshida","year":"2009","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E5537","DOI":"10.1073\/pnas.1414665111","article-title":"Bnip3 mediates doxorubicin-induced cardiac myocyte necrosis and mortality through changes in mitochondrial signaling","volume":"111","author":"Dhingra","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/cvr\/cvq361","article-title":"Mechanism of anthracycline-mediated down-regulation of GATA4 in the heart","volume":"90","author":"Park","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7546","DOI":"10.1158\/0008-5472.CAN-05-1197","article-title":"Galectin-3 Inhibits Tumor Necrosis Factor\u2013Related Apoptosis-Inducing Ligand\u2013Induced Apoptosis by Activating Akt in Human Bladder Carcinoma Cells","volume":"65","author":"Oka","year":"2005","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.1158\/0008-5472.CAN-04-0336","article-title":"Endogenous Galectin-3 Determines the Routing of CD95 Apoptotic Signaling Pathways","volume":"64","author":"Fukumori","year":"2004","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1006\/bbrc.1998.8708","article-title":"Regulation of Cellular Adhesion to Extracellular Matrix Proteins by Galectin-3","volume":"246","author":"Ochieng","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0014-5793(00)01547-7","article-title":"Galectin-3 overexpression protects from cell damage and death by influencing mitochondrial homeostasis","volume":"473","author":"Matarrese","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11897-010-0004-x","article-title":"Galectin-3 in cardiac remodeling and heart failure","volume":"7","author":"Yu","year":"2010","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_19","first-page":"1199","article-title":"Galectin-3 expression in human atherosclerotic lesions","volume":"152","author":"Nachtigal","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1093\/glycob\/cwt006","article-title":"Inhibition of galectin-3 reduces atherosclerosis in apolipoprotein E-deficient mice","volume":"23","author":"MacKinnon","year":"2013","journal-title":"Glycobiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"647","DOI":"10.3892\/mmr.2017.6646","article-title":"Modified citrus pectin inhibits galectin-3 function to reduce atherosclerotic lesions in apoE-deficient mice","volume":"16","author":"Lu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"287","DOI":"10.33594\/000000220","article-title":"Galectin-3: A Cardiomyocyte Antiapoptotic Mediator at 24-Hour Post Myocardial Infarction","volume":"54","author":"Hashmi","year":"2020","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1159\/000494539","article-title":"Myocardial Ischemia Reperfusion Injury: Apoptotic, Inflammatory and Oxidative Stress Role of Galectin-3","volume":"50","author":"Hashmi","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1093\/eurjhf\/hfp097","article-title":"Galectin-3: A novel mediator of heart failure development and progression","volume":"11","author":"Voors","year":"2009","journal-title":"Eur. J. Heart Fail."},{"key":"ref_25","first-page":"2927","article-title":"Biomarkers and heart disease","volume":"18","author":"Sun","year":"2014","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_26","first-page":"59","article-title":"The Impact of Galectin-3 Inhibition on Aldosterone-Induced Cardiac and Renal Injuries","volume":"3","author":"Calvier","year":"2015","journal-title":"JACC: Heart Fail."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.carpath.2014.12.001","article-title":"Galectin-3 is expressed in the myocardium very early post\u2013myocardial infarction","volume":"24","author":"Hashmi","year":"2015","journal-title":"Cardiovasc. Pathol."},{"key":"ref_28","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_29","first-page":"241","article-title":"Molecular mechanism of doxorubicin-induced cardiomyopathy\u2014An update, Eur","volume":"818","author":"Renu","year":"2018","journal-title":"J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.3389\/fphar.2018.01262","article-title":"Updates in anthracycline-mediated cardiotoxicity","volume":"9","author":"Nebigil","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_31","first-page":"1597012","article-title":"Role of Oxidation-Dependent CaMKII Activation in the Genesis of Abnormal Action Potentials in Atrial Cardiomyocytes: A Simulation Study","volume":"2020","author":"Zhao","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1136\/heartjnl-2017-312103","article-title":"Anthracycline cardiotoxicity: An update on mechanisms, monitoring and prevention","volume":"104","author":"Henriksen","year":"2017","journal-title":"Heart"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"344","DOI":"10.33594\/000000381","article-title":"Galectin-3 Possesses Anti-Necroptotic and Anti-Apoptotic Effects in Cisplatin-Induced Acute Tubular Necrosis","volume":"55","author":"Jagadeesh","year":"2021","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3114","DOI":"10.1158\/0008-5472.CAN-05-3750","article-title":"Galectin-3 Regulates Mitochondrial Stability and Antiapoptotic Function in Response to Anticancer Drug in Prostate Cancer","volume":"66","author":"Fukumori","year":"2006","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15819","DOI":"10.1074\/jbc.M200154200","article-title":"Galectin-3 translocates to the perinuclear membranes and inhibits cytochrome c release from the mitochondria. A role for synexin in galectin-3 translocation","volume":"277","author":"Yu","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"46663","DOI":"10.18632\/oncotarget.16944","article-title":"Autophagy and mitophagy in the context of doxorubicin-induced cardiotoxicity","volume":"8","author":"Koleini","year":"2017","journal-title":"Oncotarget."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/med.21280","article-title":"Doxorubicin-Induced Cardiotoxicity: From Bioenergetic Failure and Cell Death to Cardiomyopathy","volume":"34","author":"Carvalho","year":"2013","journal-title":"Med. Res. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hsueh, Y.-J., Chen, Y.-N., Tsao, Y.-T., Cheng, C.-M., Wu, W.-C., and Chen, H.-C. (2022). The Pathomechanism, Antioxidant Biomarkers, and Treatment of Oxidative Stress-Related Eye Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031255"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1161\/01.RES.54.3.277","article-title":"Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase","volume":"54","author":"Jolly","year":"1984","journal-title":"Circ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1146\/annurev.immunol.15.1.351","article-title":"Redox regulation of cellular activation","volume":"15","author":"Nakamura","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0014-4827(03)00211-8","article-title":"Reconstitution of galectin-3 alters glutathione content and potentiates TRAIL-induced cytotoxicity by dephosphorylation of Akt","volume":"288","author":"Lee","year":"2003","journal-title":"Exp. Cell Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1111\/j.1432-2277.2008.00705.x","article-title":"A Role for galectin-3 in renal tissue damage triggered by ischemia and reperfusion injury","volume":"21","author":"Bertocchi","year":"2008","journal-title":"Transpl. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.4049\/jimmunol.154.7.3479","article-title":"A human lectin, galectin-3 (epsilon bp\/Mac-2), stimulates superoxide production by neutrophils","volume":"154","author":"Yamaoka","year":"1995","journal-title":"J. Immunol."},{"key":"ref_44","first-page":"1016","article-title":"Expression and function of galectin-3, a beta-galactoside-binding lectin, in human monocytes and macrophages","volume":"147","author":"Liu","year":"1995","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3409\/fb_68-2.09","article-title":"Galectin-3 Deficiency Reduces Cardiac and Renal Antioxidant Capacity in Mice","volume":"68","author":"Borozan","year":"2020","journal-title":"Folia Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/0022-2828(80)90081-4","article-title":"Role of oxygen in the cellular damage induced by re-oxygenation of hypoxic heart","volume":"12","author":"Guarnieri","year":"1980","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"819310","DOI":"10.1155\/2012\/819310","article-title":"Characterization of Blood Oxidative Stress in Type 2 Diabetes Mellitus Patients: Increase in Lipid Peroxidation and SOD Activity","volume":"2012","author":"Bandeira","year":"2012","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1177\/147323001204000235","article-title":"Increase in Total Antioxidant Capacity of Plasma despite High Levels of Oxidative Stress in Uncomplicated Type 2 Diabetes Mellitus","volume":"40","author":"Savu","year":"2012","journal-title":"J. Int. Med. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mukaro, V.R., Bylund, J., Hodge, G., Holmes, M., Jersmann, H., Reynolds, P.N., and Hodge, S. (2013). Lectins Offer New Perspectives in the Development of Macrophage-Targeted Therapies for COPD\/Emphysema. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056147"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1161\/HYPERTENSIONAHA.115.05876","article-title":"Galectin-3 Blockade Inhibits Cardiac Inflammation and Fibrosis in Experimental Hyperaldosteronism and Hypertension","volume":"66","author":"Calvier","year":"2015","journal-title":"Hypertension"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"110071","DOI":"10.1016\/j.biopha.2020.110071","article-title":"Modified citrus pectin ameliorates myocardial fibrosis and inflammation via suppressing galectin-3 and TLR4\/MyD88\/NF-\u03baB signaling pathway","volume":"126","author":"Xu","year":"2020","journal-title":"Biomed Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9607","DOI":"10.1038\/s41598-019-46119-6","article-title":"Myocardial Injury After Ischemia\/Reperfusion Is Attenuated by Pharmacological Galectin-3 Inhibition","volume":"9","author":"Ibarrola","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"524826","DOI":"10.3389\/fimmu.2020.524826","article-title":"Epithelial Cell-Associated Galectin-3 Activates Human Dendritic Cell Subtypes for Pro-Inflammatory Cytokines","volume":"11","author":"Schroeder","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3389\/fimmu.2017.00048","article-title":"Cell Intrinsic Galectin-3 Attenuates Neutrophil ROS-Dependent Killing of Candida by Modulating CR3 Downstream Syk Activation","volume":"8","author":"Wu","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1189\/jlb.3A0116-026RR","article-title":"Galectin-3\u2013null mice display defective neutrophil clearance during acute inflammation","volume":"101","author":"Wright","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_56","first-page":"306","article-title":"Embryonic implantation in galectin 1\/galectin 3 double mutant mice","volume":"211","author":"Colnot","year":"1998","journal-title":"Dev. Dyn. Off. Publ. Am. Assoc. Anat."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12479\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:56:40Z","timestamp":1760144200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,18]]},"references-count":56,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms232012479"],"URL":"https:\/\/doi.org\/10.3390\/ijms232012479","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,18]]}}}