Protocatechuic acid ethyl ester (150 mg/kg) significantly reduced doxorubicin-induced cardiotoxicity markers including lactate dehydrogenase (p<0.01) and aspartate aminotransferase (p<0.001) in rats.
Does protocatechuic acid ethyl ester prevent doxorubicin-induced cardiotoxicity in male Wistar rats?
Protocatechuic acid ethyl ester mitigates doxorubicin-induced cardiotoxicity in rats, likely through alleviating oxidative stress.
Abstract Doxorubicin, an anti-neoplastic agent, is linked with a risk of cardiotoxicity following acute or cumulative doses. Protocatechuic acid ethyl ester, as a natural phenolic acid derivative, inhibits a prolyl hydroxylase enzyme with iron-chelating and antioxidative properties. This study evaluated the effects of protocatechuic acid ethyl ester on cardiotoxicity induced by doxorubicin in an animal model. Male Wistar rats were pretreated orally with 50, 75, and 150 mg/kg of protocatechuic acid ethyl ester for 14 days. Cardiotoxicity was induced by the acute injection of doxorubicin (20 mg/kg) on the 10th day. Recording of the electrocardiogram, assessment of serum parameters of aspartate aminotransferase, lactate dehydrogenase, creatine phosphokinase-MB, malondialdehyde and total antioxidant capacity as ferric reducing antioxidant power, and histopathological inspection of heart tissues were performed. Protocatechuic acid ethyl ester at all doses prevented the increase in heart rate and the decrease in the R-R interval induced by doxorubicin. Higher doses of protocatechuic acid ethyl ester (75 and 150 mg/kg) were able to improve most of the serum and tissue parameters of cardiac injury. Protocatechuic acid ethyl ester at a dose of 150 mg/kg significantly reduced lactate dehydrogenase (p<0.01), aspartate aminotransferase, creatine phosphokinase-MB, and heart weight (p<0.001) and improved histopathological changes. It markedly reversed oxidative insult through decreasing malondialdehyde (p<0.01) and increasing ferric reducing antioxidant power (p<0.05). Findings of this study indicated that protocatechuic acid ethyl ester has noteworthy potential to mitigate the cardiotoxicity associated with doxorubicin, possibly through alleviating oxidative stress.
Safaeian et al. (2026) studied Doxorubicin-induced cardiotoxicity. Protocatechuic acid ethyl ester vs. Doxorubicin alone was evaluated on Cardiotoxicity parameters (heart rate, R-R interval, serum markers, histopathology). Protocatechuic acid ethyl ester (150 mg/kg) significantly reduced doxorubicin-induced cardiotoxicity markers including lactate dehydrogenase (p<0.01) and aspartate aminotransferase (p<0.001) in rats.