{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:17:52Z","timestamp":1788016672482,"version":"build-2784847793"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Background:<\/jats:title>\n \n Administration of doxorubicin (DOX), an effective anticancer drug, is associated with cardiotoxicity. Protocatechuic acid ethyl ester (PCAE) is a natural phenolic acid derivative with antioxidant, iron-chelating capability and prolyl hydroxylase inhibitory effects. This\n in vitro<\/jats:italic>\n investigation tested whether PCAE could protect against toxicity induced by doxorubicin in cardiomyocytes and compared its effects with those of protocatechuic acid (PCA).\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n After evaluation of the cytotoxicity of PCAE (1\u2013100 \u00b5M) and DOX (0.125\u20138 \u00b5M) on H9C2 cardiomyocytes, the cells were exposed to DOX (2 \u03bcM) following 24 h pretreatment with PCAE (1\u2013100 \u00b5M). MTT assay was done to estimate the cytotoxicity or cell viability. The level of intracellular reactive oxygen species (ROS) was examined by fluorescence assay. The ferric reducing antioxidant power (FRAP) assay was performed as a measure of antioxidant capacity. Glutathione depletion assay was performed using 5,5-dithiobis-2-nitrobenzoic acid.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n PCAE (1\u2013100 \u00b5M) had no inhibitory effect on the survival rate of cardiomyocytes after 24-hour incubation. Pretreatment with PCAE at 10\u2013100 \u03bcM significantly prevented cytotoxicity of DOX using MTT test. PCAE declined the ROS level (at 1\u2013100 \u00b5M) and glutathione depletion (at 80 and 100 \u03bcM) and raised the FRAP level (at 20\u2013100 \u03bcM). These protective and antioxidant effects were significantly more potent than those of PCA activities.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n PCAE showed antioxidant and cytoprotective activities against toxicities caused by DOX in cardiomyocytes more potent than those of PCA. PCAE may be a potential candidate for prevention and treatment of DOX-induced cardiotoxicity, which requires further\n in vivo<\/jats:italic>\n and clinical researches.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/ijpvm.ijpvm_10_25","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:00:21Z","timestamp":1788015621000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Preventive Effect of Protocatechuic Acid Ethyl Ester against Doxorubicin-Induced Toxicity in Cardiomyocytes"],"prefix":"10.4103","volume":"17","author":[{"given":"Leila","family":"Safaeian","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 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