Ellagic Acid Attenuates Oxidative Stress and Improves Cardiovascular Function Following Myocardial Infarction in Ovariectomized Rats

Estrogen deficiency is linked to elevated oxidative stress and reduced nitric oxide (NO) production and bioavailability. Furthermore, myocardial infarction (MI) is a major cause of fibrosis and heart failure. This study hypothesized that ellagic acid (EA), a natural antioxidant compound, improves post-myocardial infarction outcomes in ovariectomized rats by reducing reactive oxygen species (ROS) and pro-inflammatory cytokines, and increasing NO, resulting in decreased cardiac fibrosis. MI was induced in bilateral ovariectomized Wistar rats via coronary artery ligation. EA (30 mg/kg) was orally administered by gavage daily for four weeks. Hemodynamic parameters were measured through carotid artery cannulation. Picrosirius red staining was used to assess collagen deposition and determine the infarction size. Matrix Metalloprotease-8 (MMP-8) levels were measured by immunofluorescence, while nitric oxide (NO) and superoxide anion production were quantified in situ by fluorescence. Inflammatory cytokines were quantified by ELISA. The results confirmed ventricular dysfunction and increased total collagen deposition induced by MI. Oral administration of EA reduced myocardial lesion size, improved hemodynamic parameters, and decreased total collagen deposition. Mechanistically, EA reduced cardiac levels of MMP-8, interleukin-6 (IL-6), and superoxide anion production, and increased NO bioavailability. In conclusion, EA was demonstrated as a potent compound capable of attenuating cardiac fibrosis and ventricular dysfunction by reducing collagen deposition, improving hemodynamic parameters, and providing anti-inflammatory and antioxidant effects following myocardial infarction in ovariectomized rats.