Key result
Protocatechuic acid ethyl ester prevents doxorubicin cytotoxicity in cardiomyocytes more potently than protocatechuic acid.
Why the study?
Doxorubicin administration is associated with cardiotoxicity, and the protective effects of protocatechuic acid ethyl ester against this toxicity in cardiomyocytes were not established.
Does protocatechuic acid ethyl ester prevent doxorubicin-induced toxicity in cardiomyocytes?
Does protocatechuic acid ethyl ester prevent doxorubicin-induced toxicity in cardiomyocytes?
p-value: p=<0.001
PCAE demonstrates potent in vitro cytoprotective and antioxidant properties against doxorubicin-induced cardiotoxicity, establishing a foundation for future in vivo and clinical research.
PCAE mitigated doxorubicin cytotoxicity in rat cardiomyocytes in vitro; hypothesis-generating and should not yet change clinical practice.
Background: 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 in vitro investigation tested whether PCAE could protect against toxicity induced by doxorubicin in cardiomyocytes and compared its effects with those of protocatechuic acid (PCA). Methods: After evaluation of the cytotoxicity of PCAE (1–100 µM) and DOX (0.125–8 µM) on H9C2 cardiomyocytes, the cells were exposed to DOX (2 μM) following 24 h pretreatment with PCAE (1–100 µM). 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. Results: PCAE (1–100 µM) had no inhibitory effect on the survival rate of cardiomyocytes after 24-hour incubation. Pretreatment with PCAE at 10–100 μM significantly prevented cytotoxicity of DOX using MTT test. PCAE declined the ROS level (at 1–100 µM) and glutathione depletion (at 80 and 100 μM) and raised the FRAP level (at 20–100 μM). These protective and antioxidant effects were significantly more potent than those of PCA activities. Conclusions: 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 in vivo and clinical researches.
No takes yet. Share an insight, caveat, or question.
Safaeian et al. (2026) studied Doxorubicin-induced cardiotoxicity. Protocatechuic acid ethyl ester (PCAE) vs. Doxorubicin alone was evaluated on Cell viability (cytotoxicity) (p=<0.001). Pretreatment with protocatechuic acid ethyl ester significantly prevented doxorubicin-induced cytotoxicity in H9C2 cardiomyocytes and demonstrated more potent antioxidant activities than protocatechuic acid.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: