Diosmetin exerts cardioprotective effect on myocardial ischaemia injury in neonatal rats by decreasing oxidative stress and myocardial apoptosis.

Abstract

Myocardial injury caused by the myocardial ischaemia (MI) is still a troublesome condition in the clinic, including apoptosis, oxidative stress and inflammation. Diosmetin inhibits the cellular apoptosis and inflammatory response and enhances antioxidant activity. So, this study was designed to investigate the cardioprotective effects of diosmetin on MI model neonatal rats. Forty Sprague Dawley (SD) rats 7 days old were randomly divided into five groups. Four groups of rats received diosmetin (50, 100, and 200 mg/kg) or vehicle (MI group) after ischaemia. Another group received vehicle without ischaemia to serve as a control group. Rats were pretreated with diosmetin intraperitoneally for 7 days and intoxicated with isoproterenol (ISO, 85 mg/kg, sc) on the last 2 days. The expression of apoptotic molecules, myocardial systolic function index, antioxidant enzymes and myocardial enzyme was analyzed. Compared with the control group, the proliferation marker proteins of Ki67 were increased significantly (P < .05), the MI group significantly increased the cardiac apoptosis, oxidative stress and myocardial enzymes, and weakened myocardial contractility. The levels of p‐P65/P65 were increased significantly (P < .05) with decreased p‐AKT/AKT and p‐Nrf2/Nrf2 (P < .05). Nevertheless, pretreatment with diosmetin reversed these changes, especially high‐dose group. In summary, diosmetin has significant potential as a therapeutic intervention to ameliorate myocardial injury after MI and provides the rationale for further clinical studies.