Ageing exacerbates the cardiotoxicity of hydrogen peroxide through the Fenton reaction in rats

Abstract

Reactive oxygen species (ROS) are involved in the post-ischemic reperfusion syndrome of the myocardium. Moreover, ageing is associated with an increased cardiac sensitivity to both ischemia and reperfusion. The aim of the present study was to determine whether the lower tolerance of aged hearts to reperfusion could be due to an increased sensitivity to the ROS that are produced during the early phase of reperfusion. For this purpose isolated perfused hearts from adult (4 months) and aged (24 months) rats were perfused with a buffer containing 150 μM of hydrogen peroxide (H 2O 2) in presence or absence of deferoxamine mesylate (150 μM), an iron chelator. H 2O 2 perfusion was continued until left ventricular developed pressure had decreased up to 20% of its initial value. Ageing led to a significant reduction of the duration of the H 2O 2 perfusion required for inducing a 80% functional alteration. Although deferoxamine did not affect this parameter in adult rats, it significantly increased the duration of H 2O 2-perfusion in senescent hearts (control: 14.0±0.9 min vs. deferoxamine: 18.1±1.0, P<0.05). Similarly, ageing aggravated cardiac contracture induced by H 2O 2-perfusion. Again, deferoxamine, which had no effect on this parameter in young adult hearts, significantly reduced the contracture of senescent rat hearts. To conclude, our data clearly show that ageing is associated with an increased sensitivity of the myocardium to hydrogen peroxide, which is partly reversed by iron chelation. These results suggest that the iron-catalyzed Fenton reaction producing hydroxyl radicals might be greater in hearts from senescent rats than in hearts from young adults.