{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T03:29:46Z","timestamp":1778729386872,"version":"3.51.4"},"reference-count":93,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007069","name":"University of Calabria","doi-asserted-by":"publisher","award":["ex-60%"],"award-info":[{"award-number":["ex-60%"]}],"id":[{"id":"10.13039\/501100007069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Cardiac lipotoxicity plays an important role in the pathogenesis of obesity-related cardiovascular disease. The flavonoid quercetin (QUE), a nutraceutical compound that is abundant in the \u201cMediterranean diet\u201d, has been shown to be a potential therapeutic agent in cardiac and metabolic diseases. Here, we investigated the beneficial role of QUE and its derivative Q2, which demonstrates improved bioavailability and chemical stability, in cardiac lipotoxicity. To this end, H9c2 cardiomyocytes were pre-treated with QUE or Q2 and then exposed to palmitate (PA) to recapitulate the cardiac lipotoxicity occurring in obesity. Our results showed that both QUE and Q2 significantly attenuated PA-dependent cell death, although QUE was effective at a lower concentration (50 nM) when compared with Q2 (250 nM). QUE decreased the release of lactate dehydrogenase (LDH), an important indicator of cytotoxicity, and the accumulation of intracellular lipid droplets triggered by PA. On the other hand, QUE protected cardiomyocytes from PA-induced oxidative stress by counteracting the formation of malondialdehyde (MDA) and protein carbonyl groups (which are indicators of lipid peroxidation and protein oxidation, respectively) and intracellular ROS generation, and by improving the enzymatic activities of catalase and superoxide dismutase (SOD). Pre-treatment with QUE also significantly attenuated the inflammatory response induced by PA by reducing the release of key proinflammatory cytokines (IL-1\u03b2 and TNF-\u03b1). Similar to QUE, Q2 (250 nM) also significantly counteracted the PA-provoked increase in intracellular lipid droplets, LDH, and MDA, improving SOD activity and decreasing the release of IL-1\u03b2 and TNF-\u03b1. These results suggest that QUE and Q2 could be considered potential therapeutics for the treatment of the cardiac lipotoxicity that occurs in obesity and metabolic diseases.<\/jats:p>","DOI":"10.3390\/ijerph20043492","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T04:51:46Z","timestamp":1676523106000},"page":"3492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Quercetin and Its Derivative Counteract Palmitate-Dependent Lipotoxicity by Inhibiting Oxidative Stress and Inflammation in Cardiomyocytes"],"prefix":"10.3390","volume":"20","author":[{"given":"Maria Concetta","family":"Granieri","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1743-4724","authenticated-orcid":false,"given":"Carmine","family":"Rocca","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"De Bartolo","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Immacolata Cristina","family":"Nettore","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Clinica e Chirurgia, Scuola di Medicina, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3971-7378","authenticated-orcid":false,"given":"Vittoria","family":"Rago","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Romeo","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1386-3601","authenticated-orcid":false,"given":"Jessica","family":"Ceramella","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9763-838X","authenticated-orcid":false,"given":"Annaluisa","family":"Mariconda","sequence":"additional","affiliation":[{"name":"Department of Science, University of Basilicata, Viale dell\u2019Ateneo Lucano 10, 85100 Potenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6503-6942","authenticated-orcid":false,"given":"Paolo Emidio","family":"Macchia","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Clinica e Chirurgia, Scuola di Medicina, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Ungaro","sequence":"additional","affiliation":[{"name":"Istituto per l\u2019Endocrinologia e l\u2019Oncologia Sperimentale (IEOS) \u201cGaetano Salvatore\u201d, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2435-8931","authenticated-orcid":false,"given":"Maria Stefania","family":"Sinicropi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7797-7862","authenticated-orcid":false,"given":"Tommaso","family":"Angelone","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy"},{"name":"National Institute of Cardiovascular Research (INRC), 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1152\/physrev.00030.2020","article-title":"Obesity cardiomyopathy: Evidence, mechanisms, and therapeutic implications","volume":"101","author":"Ren","year":"2021","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jacc.2017.11.011","article-title":"Obesity: Pathophysiology and Management","volume":"71","author":"Gadde","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"320534","DOI":"10.1155\/2012\/320534","article-title":"Pathophysiological insights into cardiovascular health in metabolic syndrome","volume":"2012","author":"Zhang","year":"2012","journal-title":"Exp. Diabetes Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S1388-1981(02)00342-6","article-title":"Lipoapoptosis: Its mechanism and its diseases","volume":"1585","author":"Unger","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1161\/CIRCULATIONAHA.106.645614","article-title":"Cardiac steatosis in diabetes mellitus: A 1H-magnetic resonance spectroscopy study","volume":"116","author":"McGavock","year":"2007","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pasqua, T., Rocca, C., Giglio, A., and Angelone, T. (2021). Cardiometabolism as an Interlocking Puzzle between the Healthy and Diseased Heart: New Frontiers in Therapeutic Applications. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040721"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/joim.12728","article-title":"Manifestations and mechanisms of myocardial lipotoxicity in obesity","volume":"284","author":"Sletten","year":"2018","journal-title":"J. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Joseph, L.C., Barca, E., Subramanyam, P., Komrowski, M., Pajvani, U., Colecraft, H.M., Hirano, M., and Morrow, J.P. (2016). Inhibition of NAPDH Oxidase 2 (NOX2) Prevents Oxidative Stress and Mitochondrial Abnormalities Caused by Saturated Fat in Cardiomyocytes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0145750"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e291","DOI":"10.1038\/emm.2016.157","article-title":"Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes","volume":"49","author":"Ly","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/jcp.24781","article-title":"Palmitate induces ER stress and autophagy in H9c2 cells: Implications for apoptosis and adiponectin resistance","volume":"230","author":"Park","year":"2015","journal-title":"J. Cell Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1172\/JCI200422230","article-title":"PKC-theta knockout mice are protected from fat-induced insulin resistance","volume":"114","author":"Kim","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E489","DOI":"10.1152\/ajpendo.00569.2010","article-title":"Cardiomyocyte lipids impair \u03b2-adrenergic receptor function via PKC activation","volume":"300","author":"Drosatos","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1073\/pnas.0630588100","article-title":"Triglyceride accumulation protects against fatty acid-induced lipotoxicity","volume":"100","author":"Listenberger","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13997","DOI":"10.1038\/ncomms13997","article-title":"Saturated palmitic acid induces myocardial inflammatory injuries through direct binding to TLR4 accessory protein MD2","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"112413","DOI":"10.1016\/j.biopha.2021.112413","article-title":"Natural and chemical compounds as protective agents against cardiac lipotoxicity","volume":"145","author":"Yarmohammadi","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Alam, W., Rocca, C., Khan, H., Hussain, Y., Aschner, M., De Bartolo, A., Amodio, N., Angelone, T., and Cheang, W.S. (2021). Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction. Antioxidants, 10.","DOI":"10.3390\/antiox10101643"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jff.2018.11.030","article-title":"A pilot study on the nutraceutical properties of the Citrus hybrid Tacle\u00ae as a dietary source of polyphenols for supplementation in metabolic disorders","volume":"52","author":"Casacchia","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1007\/s00394-018-1609-1","article-title":"Leopoldia comosa prevents metabolic disorders in rats with high-fat diet-induced obesity","volume":"58","author":"Casacchia","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jnutbio.2019.03.019","article-title":"Quercetin and its derivative Q2 modulate chromatin dynamics in adipogenesis and Q2 prevents obesity and metabolic disorders in rats","volume":"69","author":"Nettore","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M.T., Wang, S., Liu, H., and Yin, Y. (2016). Quercetin, Inflammation and Immunity. Nutrients, 8.","DOI":"10.3390\/nu8030167"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8825387","DOI":"10.1155\/2020\/8825387","article-title":"Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine","volume":"2020","author":"Yang","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/ptr.4687","article-title":"Quercetin reduces high-fat diet-induced fat accumulation in the liver by regulating lipid metabolism genes","volume":"27","author":"Jung","year":"2013","journal-title":"Phytother. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.3945\/jn.111.157263","article-title":"Quercetin Ameliorates Cardiovascular, Hepatic, and Metabolic Changes in Diet-Induced Metabolic Syndrome in Rats","volume":"142","author":"Panchal","year":"2012","journal-title":"J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Papakyriakopoulou, P., Velidakis, N., Khattab, E., Valsami, G., Korakianitis, I., and Kadoglou, N.P. (2022). Potential Pharmaceutical Applications of Quercetin in Cardiovascular Diseases. Pharmaceuticals, 15.","DOI":"10.3390\/ph15081019"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ejps.2015.11.021","article-title":"Quercetin derivatives as novel antihypertensive agents: Synthesis and physiological characterization","volume":"82","author":"Grande","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.4155\/fmc-2017-0118","article-title":"New insights for the use of quercetin analogs in cancer treatment","volume":"9","author":"Iacopetta","year":"2017","journal-title":"Future Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107487","DOI":"10.1016\/j.intimp.2021.107487","article-title":"Cateslytin abrogates lipopolysaccharide-induced cardiomyocyte injury by reducing inflammation and oxidative stress through toll like receptor 4 interaction","volume":"94","author":"Rocca","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e13570","DOI":"10.1111\/apha.13570","article-title":"The chromogranin A1-373 fragment reveals how a single change in the protein sequence exerts strong cardioregulatory effects by engaging neuropilin-1","volume":"231","author":"Rocca","year":"2021","journal-title":"Acta Physiol. (Oxf)."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Grande, F., De Bartolo, A., Occhiuzzi, M.A., Caruso, A., Rocca, C., Pasqua, T., Carocci, A., Rago, V., Angelone, T., and Sinicropi, M.S. (2021). Carbazole and Simplified Derivatives: Novel Tools toward \u03b2-Adrenergic Receptors Targeting. Appl. Sci., 11.","DOI":"10.3390\/app11125486"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rocca, C., De Bartolo, A., Granieri, M.C., Rago, V., Amelio, D., Falbo, F., Malivindi, R., Mazza, R., Cerra, M.C., and Boukhzar, L. (2022). The Antioxidant Selenoprotein T Mimetic, PSELT, Induces Preconditioning-like Myocardial Protection by Relieving Endoplasmic-Reticulum Stress. Antioxidants, 11.","DOI":"10.3390\/antiox11030571"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4440","DOI":"10.1111\/bph.12795","article-title":"Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression","volume":"171","author":"Dong","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/000456327200900102","article-title":"Optimal Assay of LDH and \u03b1-HBD at 37 \u00b0C","volume":"9","author":"McQueen","year":"1972","journal-title":"Ann. Clin. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7734","DOI":"10.1096\/fj.201802707R","article-title":"Physiological levels of chromogranin A prevent doxorubicin-induced cardiotoxicity without impairing its anticancer activity","volume":"33","author":"Rocca","year":"2019","journal-title":"FASEB J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.3892\/etm.2017.4240","article-title":"Berberis vulgaris extract\/\u03b2-cyclodextrin complex increases protection of hepatic cells via suppression of apoptosis and lipogenesis pathways","volume":"13","author":"Ivan","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5303","DOI":"10.1111\/jcmm.14407","article-title":"Myeloid differentiation protein 1 protected myocardial function against high-fat stimulation induced pathological remodelling","volume":"23","author":"Shen","year":"2019","journal-title":"J. Cell Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"H710","DOI":"10.1152\/ajpheart.00538.2017","article-title":"miR-21-5p regulates mitochondrial respiration and lipid content in H9C2 cells","volume":"316","author":"Nasci","year":"2019","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.regpep.2004.03.010","article-title":"Gut regulatory peptides bombesin and neurotensin reduce hepatic oxidative stress and histological alterations in bile duct ligated rats","volume":"120","author":"Assimakopoulos","year":"2004","journal-title":"Regul. Pept."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.biopha.2018.02.027","article-title":"Chlorogenic acid attenuates glucotoxicity in H9c2 cells via inhibition of glycation and PKC \u03b1 upregulation and safeguarding innate antioxidant status","volume":"100","author":"Anupama","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0076-6879(94)33041-7","article-title":"Oxidative damage to proteins: Spectrophotometric method for carbonyl assay","volume":"233","author":"Reznick","year":"1994","journal-title":"Methods Enzymol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pasqua, T., Rocca, C., Lupi, F.R., Baldino, N., Amelio, D., Parisi, O.I., Granieri, M.C., De Bartolo, A., Lauria, A., and Dattilo, M. (2020). Cardiac and Metabolic Impact of Functional Foods with Antioxidant Properties Based on Whey Derived Proteins Enriched with Hemp Seed Oil. Antioxidants, 9.","DOI":"10.3390\/antiox9111066"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1432-1033.1974.tb03714.x","article-title":"Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase","volume":"47","author":"Marklund","year":"1974","journal-title":"Eur. J. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","article-title":"Catalase in vitro","volume":"105","author":"Aebi","year":"1984","journal-title":"Methods Enzymol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.fct.2014.01.027","article-title":"Multiple pathways are involved in palmitic acid-induced toxicity","volume":"67","author":"Park","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1139\/y04-065","article-title":"Diabetic cardiomyopathy: Recent evidence from mouse models of type 1 and type 2 diabetes","volume":"82","author":"Severson","year":"2004","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1475-2840-8-39","article-title":"Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: Studies using positron emission tomography","volume":"8","author":"Huisman","year":"2009","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1161\/01.CIR.100.10.1134","article-title":"Diabetes and cardiovascular disease: A statement for healthcare professionals from the American Heart Association","volume":"100","author":"Grundy","year":"1999","journal-title":"Circulation"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.2337\/diacare.27.8.1879","article-title":"The incidence of congestive heart failure in type 2 diabetes: An update","volume":"27","author":"Nichols","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.bbalip.2009.09.023","article-title":"Lipotoxicity in the heart","volume":"1801","author":"Wende","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1161\/CIRCRESAHA.116.304707","article-title":"MicroRNA-451 exacerbates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy in mice through suppression of the LKB1\/AMPK pathway","volume":"116","author":"Kuwabara","year":"2015","journal-title":"Circ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Urso, C.J., and Zhou, H. (2021). Role of CD36 in Palmitic Acid Lipotoxicity in Neuro-2a Neuroblastoma Cells. Biomolecules, 11.","DOI":"10.3390\/biom11111567"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1161\/01.RES.69.6.1476","article-title":"Morphological, biochemical, and electrophysiological characterization of a clonal cell (H9c2) line from rat heart","volume":"69","author":"Hescheler","year":"1991","journal-title":"Circ. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"627123","DOI":"10.3389\/fphar.2021.627123","article-title":"Inhibition of TLR4\/MAPKs Pathway Contributes to the Protection of Salvianolic Acid Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice","volume":"12","author":"Yang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S1388-1981(00)00028-7","article-title":"Palmitate-induced apoptosis in cardiomyocytes is mediated through alterations in mitochondria: Prevention by cyclosporin A","volume":"1485","author":"Kong","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.bbalip.2008.07.009","article-title":"Protective effect of eicosapentaenoic acid on palmitate-induced apoptosis in neonatal cardiomyocytes","volume":"1781","author":"Leroy","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Di Majo, D., Sardo, P., Giglia, G., Di Liberto, V., Zummo, F.P., Zizzo, M.G., Caldara, G.F., Rappa, F., Intili, G., and van Dijk, R.M. (2023). Correlation of Metabolic Syndrome with Redox Homeostasis Biomarkers: Evidence from High-Fat Diet Model in Wistar Rats. Antioxidants, 12.","DOI":"10.3390\/antiox12010089"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1080\/15376516.2018.1564948","article-title":"Quercetin protects cardiomyocytes against doxorubicin-induced toxicity by suppressing oxidative stress and improving mitochondrial function via 14-3-3\u03b3","volume":"29","author":"Chen","year":"2019","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.biopha.2017.04.033","article-title":"Cardioprotective mechanisms of phytochemicals against doxorubicin-induced cardiotoxicity","volume":"90","author":"Abushouk","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.phytochem.2012.11.020","article-title":"Flavonoids from Malus hupehensis and their cardioprotective effects against doxorubicin-induced toxicity in H9c2 cells","volume":"87","author":"Wang","year":"2013","journal-title":"Phytochemistry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5724973","DOI":"10.1155\/2016\/5724973","article-title":"Cardioprotective Potentials of Plant-Derived Small Molecules against Doxorubicin Associated Cardiotoxicity","volume":"2016","author":"Ojha","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_60","first-page":"364519","article-title":"Cardioprotective Effects of Quercetin in Cardiomyocyte under Ischemia\/Reperfusion Injury","volume":"2013","author":"Chen","year":"2013","journal-title":"Evid Based Complement Alternat Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1080\/10717544.2022.2058646","article-title":"Application of chitosan\/alginate nanoparticle in oral drug delivery systems: Prospects and challenges","volume":"29","author":"Li","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5529913","DOI":"10.1155\/2021\/5529913","article-title":"Quercetin Improves Cardiomyocyte Vulnerability to Hypoxia by Regulating SIRT1\/TMBIM6-Related Mitophagy and Endoplasmic Reticulum Stress","volume":"2021","author":"Chang","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4441","DOI":"10.2174\/1381612821666150803151758","article-title":"Role of Antioxidants for the Treatment of Cardiovascular Diseases: Challenges and Opportunities","volume":"21","author":"Jain","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6401","DOI":"10.1016\/j.bmcl.2013.09.054","article-title":"Biological activity of 3-chloro-azetidin-2-one derivatives having interesting antiproliferative activity on human breast cancer cell lines","volume":"23","author":"Chimento","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8597","DOI":"10.1021\/jm101252m","article-title":"Enhanced stability and intracellular accumulation of quercetin by protection of the chemically or metabolically susceptible hydroxyl groups with a pivaloxymethyl (POM) promoiety","volume":"53","author":"Kim","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.tifs.2021.11.032","article-title":"Recent advances on the improvement of quercetin bioavailability","volume":"119","author":"Kandemir","year":"2022","journal-title":"Trends Food Sci. Technol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"855","DOI":"10.3892\/mmr.2013.1276","article-title":"Palmitate induces H9c2 cell apoptosis by increasing reactive oxygen species generation and activation of the ERK1\/2 signaling pathway","volume":"7","author":"Wei","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/1476-511X-11-135","article-title":"Globular adiponectin protects H9c2 cells from palmitate-induced apoptosis via Akt and ERK1\/2 signaling pathways","volume":"11","author":"Wei","year":"2012","journal-title":"Lipids Health Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6934","DOI":"10.3892\/mmr.2017.7404","article-title":"Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stress-mediated apoptosis pathway","volume":"16","author":"Zou","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.jacc.2006.07.022","article-title":"Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy","volume":"48","author":"Cai","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.freeradbiomed.2006.06.007","article-title":"Suppression of nitrative damage by metallothionein in diabetic heart contributes to the prevention of cardiomyopathy","volume":"41","author":"Cai","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/aps.2010.31","article-title":"Improvement of mechanical heart function by trimetazidine in db\/db mice","volume":"31","author":"Li","year":"2010","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1159\/000485089","article-title":"Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species","volume":"44","author":"He","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.1007\/s00018-019-03195-1","article-title":"Progress in the emerging role of selenoproteins in cardiovascular disease: Focus on endoplasmic reticulum-resident selenoproteins","volume":"76","author":"Rocca","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12986-019-0356-5","article-title":"High-density lipoprotein ameliorates palmitic acid-induced lipotoxicity and oxidative dysfunction in H9c2 cardiomyoblast cells via ROS suppression","volume":"16","author":"Wu","year":"2019","journal-title":"Nutr. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"114209","DOI":"10.1016\/j.bcp.2020.114209","article-title":"A novel oral glucagon-like peptide 1 receptor agonist protects against diabetic cardiomyopathy via alleviating cardiac lipotoxicity induced mitochondria dysfunction","volume":"182","author":"Qian","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12937-016-0186-5","article-title":"The importance of antioxidants which play the role in cellular response against oxidative\/nitrosative stress: Current state","volume":"15","author":"Kurutas","year":"2016","journal-title":"Nutr. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.biopha.2016.12.044","article-title":"Quercetin ameliorates oxidative stress, inflammation and apoptosis in the heart of streptozotocin-nicotinamide-induced adult male diabetic rats","volume":"86","author":"Roslan","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8875729","DOI":"10.1155\/2021\/8875729","article-title":"Quercetin Reverses Cardiac Systolic Dysfunction in Mice Fed with a High-Fat Diet: Role of Angiogenesis","volume":"2021","author":"Yu","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1172\/JCI109642","article-title":"Enzymatic defenses of the mouse heart against reactive oxygen metabolites: Alterations produced by doxorubicin","volume":"65","author":"Doroshow","year":"1980","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1089\/ars.2020.8016","article-title":"Cardiac Damage in Anthracyclines Therapy: Focus on Oxidative Stress and Inflammation","volume":"32","author":"Rocca","year":"2020","journal-title":"Antioxid. Redox Signal."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Nishi, H., Higashihara, T., and Inagi, R. (2019). Lipotoxicity in Kidney, Heart, and Skeletal Muscle Dysfunction. Nutrients, 11.","DOI":"10.3390\/nu11071664"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/obr.12828","article-title":"Hypoxia-inducible factor 1-alpha (HIF-1\u03b1) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction","volume":"20","author":"Warbrick","year":"2019","journal-title":"Obes. Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1111\/bph.12475","article-title":"Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy","volume":"171","author":"Fillmore","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1002\/jcb.27643","article-title":"Inhibition of protein kinase R protects against palmitic acid-induced inflammation, oxidative stress, and apoptosis through the JNK\/NF-kB\/NLRP3 pathway in cultured H9C2 cardiomyocytes","volume":"120","author":"Mangali","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature07203","article-title":"From endoplasmic-reticulum stress to the inflammatory response","volume":"454","author":"Zhang","year":"2008","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cmet.2012.04.001","article-title":"Inflammation and lipid signaling in the etiology of insulin resistance","volume":"15","author":"Glass","year":"2012","journal-title":"Cell Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1161\/ATVBAHA.109.188813","article-title":"Activation of NF-kappaB by palmitate in endothelial cells: A key role for NADPH oxidase-derived superoxide in response to TLR4 activation","volume":"29","author":"Maloney","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0167-5273(99)00190-4","article-title":"Inflammatory mediators in heart failure","volume":"72","author":"Niebauer","year":"2000","journal-title":"Int. J. Cardiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/00001573-199705000-00002","article-title":"The role of cytokines in disease progression in heart failure","volume":"12","author":"Shan","year":"1997","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0167-5273(99)00186-2","article-title":"The role of inflammatory mediators in chronic heart failure: Cytokines, nitric oxide, and endothelin-1","volume":"72","author":"Sharma","year":"2000","journal-title":"Int. J. Cardiol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Forney, L.A., Lenard, N.R., Stewart, L.K., and Henagan, T.M. (2018). Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030895"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2147\/JIR.S228361","article-title":"Modulation of Chronic Inflammation by Quercetin: The Beneficial Effects on Obesity","volume":"13","author":"Sato","year":"2020","journal-title":"J. Inflamm. Res."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/20\/4\/3492\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:58Z","timestamp":1760121478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/20\/4\/3492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,16]]},"references-count":93,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijerph20043492"],"URL":"https:\/\/doi.org\/10.3390\/ijerph20043492","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,16]]}}}