Protocatechuic Acid Ethyl Ester Protects Against Doxorubicin-induced Cardiotoxicity in Rats

Abstract

Background 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. Methods 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 10 th 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. Results 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). Conclusions 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.