Pharmacodynamics of ellagic acid on cardiac troponin-T, lyosomal enzymes and membrane bound ATPases: mechanistic clues from biochemical, cytokine and in vitro studies

Abstract

The anti lipid peroxidative and antioxidant effects of ellagic acid against isoproterenol-induced myocardial infarcted rats were reported previously. This study was designed to evaluate the protective effects of ellagic acid on the levels of cardiac troponin-T, lysosomal enzymes, and membrane bound ATPases along with the role of pro inflammatory cytokine. Male albino Wistar rats were pretreated with ellagic acid (7.5 and 15 mg/kg body weight) daily for a period of 10 days. After the pretreatment period isoproterenol (100mg/kg) was subcutaneously injected to rats twice at an interval of 24h. The protective effects of pretreatment with ellagic acid were measured by biochemical analysis and reverse transcriptase polymerase chain reaction. Evidence of myocardial infarction in isoproterenol induced rats included significant increase in the serum level of cardiac troponin-T and decreased levels of creatine kinase and lactate dehydrogenase in heart tissue homogenate .The pretreatment with ellagic acid restored the levels of cardiac markers in the serum and heart tissue homogenates. The activities of lysosomal enzymes (β-d-glucuronidase, β-N-acetyl glucosaminidase, β-galactosidase, cathepsin-d and acid phosphatase) were increased significantly in the serum and heart tissue of isoproterenol-induced rats. The activity of Na(+)/K(+)ATPase declined while the activities of Ca(2+)ATPase and Mg(2+)ATPase were increased significantly in the heart of isoproterenol-induced rats. Pretreatment with ellagic acid restored the activities of lysosomal enzymes and membrane bound ATPases. The higher expressions of pro-inflammatory cytokines such as interleukin-1β, interleukin-6 and tumour necrosis factor-α in the isoproterenol-induced rats were controlled by the pretreatment with ellagic acid. Our results imply that oral pretreatment with ellagic acid protects the heart lysosomal membrane against isoproterenol-induced cardiac damage. The observed effects might be due to the free radical scavenging, membrane stabilizing and anti-inflammatory properties of ellagic acid.