Icariin attenuates isoproterenol-induced cardiac toxicity in Wistar rats via modulating cGMP level and NF-κB signaling cascade.

Icariin, a major component of Epimedium species, was evaluated using isoproterenol (ISO)-induced cardiotoxicity in Wistar rats. Rats were treated with icariin at the doses of 1, 5, and 10 mg kg-1 orally for 15 days. Afterward, rats were administered with ISO (85 mg kg-1, subcutaneous) on 14th and 15th day to produce cardiac injury. Sildenafil (0.7 mg kg-1, intraperitoneal) was used as a positive reference to compare the effects of icariin. ISO-treated rats showed significant changes in hemodynamic parameters. Elevated levels of cardiac troponin T, nitric oxide, and tumor necrosis factor-alpha in serum, positive expression of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase in cardiac tissue, and a decrease in serum level of interleukin-10, manifested inflammation and associated cardiac injury. However, pretreatment with icariin and sildenafil significantly prevented the hemodynamic fall and showed improved contractile and lusitropic states. Furthermore, pretreatment groups also showed a reversal of other toxicity markers to normal. Additionally, pretreatment with icariin and sildenafil significantly increased the myocardial cyclic guanosine monophosphate (cGMP) levels. Our results thus indicated the potential role of icariin in the restoration of the ISO-induced cardiac toxicity and restored membrane integrity through modulation of cGMP and NF-κB signaling.

Fenofibrate ameliorates neural, mechanical, chemical, and electrical alterations in the murine model of heart failure.

Heart failure (HF) is a leading cause of hospitalization across the world and is known to cause ill-health and heavy economic losses. In the present study, a rat model of isoproterenol (ISO, 85 mg/kg subcutaneously for two subsequent days) induced HF was developed. ISO induces HF by its direct effect, that is, rise in left ventricular end-diastolic pressure (mechanical) and indirectly by altering the baroreflex (neural), electrocardiography (electrical), and development of oxidative stress and hyperlipidemia (chemical). Fenofibrate, a hypolipidemic drug, which ameliorates myocardial energy metabolism was seen to improve the both ISO-induced oxidative stress and lipid profile and consequently improved Baroreflex Sensitivity (BRS), partial ventricular functions, and cardiac hypertrophy. Therefore, our result suggests that fenofibrate treatment protected the heart by alleviating the ISO-induced effects, that is, neural, mechanical, electrical, and chemical alterations.