Mechanistic Clues in the Protective Effect of Ellagic Acid Against Apoptosis and Decreased Mitochondrial Respiratory Enzyme Activities in Myocardial Infarcted Rats

Abstract

Our previous study described the cardioprotective effects of ellagic acid in an isoproterenol-induced myocardial infarction model. In this study, we are reporting the mechanism of protective action of ellagic acid with respect to apoptosis and mitochondrial respiratory enzymes. Ellagic acid (7.5 and 15 mg/kg) was administered orally as a pretreatment for 10 days. Then, isoproterenol (100 mg/kg) was injected subcutaneously to rats at an interval of 24 h for 2 days. Myocardial infarction was quantified by planimetry. Apoptosis was measured by apoptotic gene expressions. The levels of mitochondrial respiratory enzymes were also measured. Isoproterenol-induced myocardial infarcted rats showed increased infarct size, a decrease in myocardial expression of the Bcl-2 gene and an increase in myocardial expression of the BAX gene. Fas ligand and caspases were markedly elevated along with compromised respiratory marker enzymes in isoproterenol-induced rats. Ellagic acid pretreatment reduced the infarct size, regulated apoptotic gene expressions and enhanced the activities of mitochondrial respiratory marker enzymes and cell viability, thereby protecting the myocardium against isoproterenol-induced myocardial infarction. The decreased infarct size associated with inhibited apoptosis and increased respiratory marker enzymes provide insight on the role of ellagic acid in antiapoptotic mechanism, and it may be the reason for its cardioprotective activity.

Rosuvastatin and ellagic acid protect against isoproterenol-induced myocardial infarction in hyperlipidemic rats

“…Here, rosuvastatin reduced cardiomyocyte apoptosis by Bax downregulation and mild Bcl-2 upregulation. On the other hand, pretreatment with ellagic acid was unable to significantly protect the cardiomyocytes from apoptosis which contrasts with a report of anti-apoptotic effect of ellagic acid on rats with MI (Mari Kannan and Darlin Quine, 2012). In such report, ellagic acid was administered in smaller doses (7.5 & 15 mg/kg/day) for a shorter period (10 days), which could account for the disagreement with our study.…”

“…Rosuvastatin has been reported to prevent MI induced experimentally by occlusion of left coronary artery in rats (Dourado et al, 2011). Ellagic acid is a polyphenolic compound that is found in strawberries, pomegranates and grapes (Mari Kannan and Darlin Quine, 2012). It possesses a number of biological activities such as antioxidant, antihyperlipidemic, anti-inflammatory and hepatoprotective effects (Rogerio et al, 2008).…”

Vanillic acid prevents altered ion pumps, ions, inhibits Fas-receptor and caspase mediated apoptosis-signaling pathway and cardiomyocyte death in myocardial infarcted rats

“…Hence, we evaluated the 595 molecular mechanism of vanillic acid on Fas-receptor and caspase 596 mediated apoptosis-signaling pathway in ISO induced myocardial 597 infarcted rats. 598 Previous studies have revealed that oxidative stress causes car-599 diomyocyte apoptosis in ISO induced myocardial infarcted rats 600 [24]. As reported earlier [24], we also observed increased expres- …”

“…598 Previous studies have revealed that oxidative stress causes car-599 diomyocyte apoptosis in ISO induced myocardial infarcted rats 600 [24]. As reported earlier [24], we also observed increased expres- …”

Thymol attenuates altered lipid metabolism in β-adrenergic agonist induced myocardial infarcted rats by inhibiting tachycardia, altered electrocardiogram, apoptosis and cardiac hypertrophy

“…The rat sense and anti-sense primers were used. GAPDH: 5′ TTC TTG TGC AGT GCC AGC CTC GTC-3′ and 5′ TAG GAA CAC GGA AGG CCA TGC CAG-3′; Bax: TTC ATC CAG GAT CGA GCA GA and GCA AAG TAG AAG GCA ACG; Bcl-2: CTG GTG GAC AAC ATC GCT CTG and GGT CTG CTG ACC TCA CTT GTG (Kannan & Quine, 2011b). The reverse transcription polymerase chain reaction products were electrophoresed on a 1% agarose gel and visualized by staining with ethidium bromide.…”