RESUMEN
The roles of oxidative stress on nuclear factor (NF)κB activity and cardiomyocyte apoptosis during heart failure were examined using the antioxidant Nacetylcysteine (NAC). Heart failure was established in Japanese white rabbits with intravenous injections of doxorubicin, with ten rabbits serving as a control group. Of the rabbits with heart failure, 12 were not treated (HF group) and 13 received NAC (NAC group). Cardiac function was assessed using echocardiography and hemodynamic analysis. Myocardial cell apoptosis, apoptosisrelated protein expression, NFκBp65 expression and activity, total antioxidative capacity (tAOC), 8isoprostaglandin F2α (8isoPGF2α) expression and glutathione (GSH) expression levels were determined. In the HF group, reduced tAOC, GSH levels and Bcl2/Bax ratios as well as increased 8isoPGF2α levels and apoptosis were observed (all P<0.05), which were effects that were attenuated by the treatment with NAC. NFκBp65 and iNOS levels were significantly higher and the PIκBα levels were significantly lower in the HF group; expression of all three proteins returned to preHF levels following treatment with NAC. Myocardial cell apoptosis was positively correlated with left ventricular end-diastolic pressure (LVEDP), NFκBp65 expression and 8isoPGF2α levels, but negatively correlated with the maximal and minimal rates of increase in left ventricular pressure (+dp/dtmax and dp/dtmin, respectively) and the Bcl2/Bax ratio (all P<0.001). The 8isoPGF2α levels were positively correlated with LVEDP and negatively correlated with +dp/dtmax and dp/dtmin (all P<0.001). The present study demonstrated that NAC increased the antioxidant capacity, decreased the NFκB activation and reduced myocardial cell apoptosis in an in vivo heart failure model.