Electrophysiological investigation of the effect of ellagic acid on cardiac hypertrophy

Objective: The aim of this study was to investigate whether chronic EA application has any effect on the changes in contractile function and Ca2+ regulation of cardiomyocytes in pathologic cardiac hypertrophy and to examine the possible roles of reactive oxygen species (ROS) in this process. Method: The cardiac hypertrophy model was performed by administering isoproterenol (ISO), which is a β-AR agonist. During the 4-week experimental period, ISO (5mg/kg) was injected subcutaneously into the ISO and ISO+EA groups. EA (20 mg/kg) was administered to the ISO+EA and C+EA groups by gavage. At the end of this period, fractional shortening, intracellular Ca2+ transients, SR Ca2+ content, and Ca2+ currents of isolated ventricular myocytes were recorded. Protein expression levels were determined by western blotting method and protein carbonyl was measured by colorimetric assay kit. Results: In the ISO group, the contraction rate and the amplitude of contraction decreased, whereas the EA application improved both the amplitude and rate of the contraction. EA application was not only restored the ISO-induced increase in diastolic Ca2+ levels but also significantly improved the decrease in amplitude and decay rate of Ca2+ transient. The Ca2+ channel current which decreased in the ISO group was found to be increased with EA application. When the protein expressions were examined, it was found that ANP, CaMKII, SERCA and p-PLB expressions were increased in the ISO group and the expression of proteins other than SERCA was decreased with EA application. In addition, the application of ISO did not alter the expression of Nox2 protein, whereas it significantly increased the expression of p-22phox and p-47phox subunits. The expression of the p-22phox subunit was decreased with the EA application. In addition, EA decreased protein oxidation which was found to be increased in the ISO group. Conclusions: Increased ROS may cause deterioration of Ca2+ regulation and contractile activity in myocytes, whereas chronic EA administration may prevent Ca2+ dysregulation and functional abnormalities associated with pathological cardiac hypertrophy.