Abstract
The role of oxidative injury and inflammatory response in cardiovascular diseases and heart failure has been well-acknowledged. This study evaluated the protective effect of umbelliferone (UMB), a coumarin with promising radical scavenging and anti-inflammatory activities, on myocardial injury induced by isoproterenol (ISO) in rats. Rats received 50 mg/kg UMB orally for 14 days and 85 mg/kg ISO twice at an interval of 24 h. Administration of ISO elevated serum troponin I, creatine kinase-MB and lactate dehydmgenase, and caused histopathological alterations, including degeneration, fatty vacuolation, myolysis, and atrophy of myocardial fibers. Malondialdehyde (MDA), nitric oxide (NO), nuclear factor-kappaB (NF-kappa B) p65, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1 beta were increased, whereas reduced glutathione (GSH), superoxide dismutase (SOD), and catalase were decreased in ISO-administered rats. UMB effectively ameliorated myocardial injury, alleviated cardiac function markers, MDA, NO, NF-kappa B p65, and the inflammatory mediators, and enhanced cellular antioxidants. Bax, caspase-3, and 8-OHdG were decreased, and Bcl-2 was increased in ISO-administered rats treated with UMB. In addition, UMB upregulated nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 in the heart of ISO-administered rats. In conclusion, UMB can protect the myocardium from oxidative injury, inflammatory response, and cell death induced by ISO by upregulating Nrf2/HO-1 signaling and antioxidants.