Human failing heart left ventricle is more protected than right ventricle versus oxidative stress

Increasing evidences suggest that oxidative stress plays a critical role in the development of human heart failure. During pathophysiological conditions, the balance between free radicals and antioxidants may shift towards a relative increase of free radicals resulting in oxidative stress. Few and conflicting data are available on antioxidant defences in human failing hearts and they are limited to left (LV) ventricle. The aim of this sfudy was to investigate the source of free radicals and antioxi6ant enzyme activities in the right (RV) and LV ventricles of human failing hearts and their mutual relationship. We found a significant increase in NADPH oxidase activity in both ventricles of faitng hearts. Protein expression and catalytic activity of catalase (CAT), glutathione peroxidase (Gpx), manganese superoxide dismutase (Mn-SOD) were also evaluated. Despite unchanged protein expression of all enzymes, significant enhances in GPx and CAT activity were observed. A significant decrease in Mn-SOD activity was detected. Interestingly, a significant correlation was found between the values of GPx and catalase activify in LV and RV of the same heart. In addition, an increase in NADPH oxidase-dependent superoxide production positively correlated with the activation of both antioxidant enzymes, showing a more protection of the LV with respect RV. Consistent with this finding MDA levels, measured as an indirect index of oxidative stress, were signifìcantly higher in the RV than LV. Our findings suggest that a similar adaptive response occurs in human failing LV and RV supporting the hypothesis of an antioxidant enzymes upregulation probably due to post-transductional modifications induced by an increased NADPH-oxidase superoxide generation. Moreover, human failing LV appeared more protected than RV versus oxidative stress clamage.