Heart failure have been observed, such as research that revealed that despite the fact that
Heart failure have been observed, such as research that revealed that even though African-American individuals are at a greatest danger of creating heart failure with subsequent hospitalization (5), the prevalence of atrial fibrillation in patients hospitalized with heart failure was higher in white patients (6). Oxidative pressure has a vital role within the occurrence and improvement of heart failure, which can be characterized by contractile dysfunction (7). In patients with heart failure and in vivo models, excessive reactive oxygen species (ROS) production in the myocardium, accompanied by systemic inflammation, have been observed (8,9). In addition, it has been demonstrated that the amount of oxidative pressure is related with the severity of heart failure and the grade of cardiac function (ten). Oxidative stress may induce myocardial cell apoptosis, resulting in cardiac tissue damage and also the subsequent deterioration of hemodynamics (8,11). Inflammation-related nuclear aspect (NF)- B signaling and its correlation with apoptosis have already been proposed as a mechanism underlying the pathogenesis of heart failure (12). Despite the fact that a cardioprotective role for NF- B in acute hypoxia has been observed, different research have demonstrated that prolonged NF- B activation induces myocardial injury (13,14). NF- B is really a transcription element that regulates the expression of proinflammatory cytokines, including interleukin (IL)-1, IL-6 and tumor necrosis factor- (TNF-), too as genes associated with apoptosis (e.g. p53) (14). Inside a previous study in NF- B-null mice, improved cardiac function following myocardial infarction was observed (15). Oxidative stress could activate NF- B and initiate the transcription of several pro-apoptotic genes, which includes Bax, Fas and FasL, inducing myocardial cell apoptosis and promoting heart failure. A ntioxidant therapy attenuates ischem ia-reperf usion-induced apoptosis of ca rdiomyocytes (16). N-acetylcysteine (NAC), the precursor of glutathione (GSH), increases the intracellular content of GSH, stabilizes the cell membrane, protects the cellular viability and directlyCorrespondence to: Dr Xiao-Yan Wu, Division of Cardiology,Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, Hubei 430071, P.R. China E-mail: xiaoyan5233yeah.net apoptosis, reactive oxygen speciesKey words: N-acetylcysteine, nuclear element B, heart failure,WU et al: ROS, NF- B AND CARDIOMYOCYTE APOPTOSISscavenges ROS (16). As a result, in ischemia-reperfusion injury, NAC is able to prevent ROS-induced apoptosis (17), and in ischemic heart failure, NAC decreased superoxide anion levels and restored cardiomyocyte contractility (18). The present study aimed to establish the impact of NAC on oxidative stress, myocardial apoptosis and NF- B activation. An in vivo heart failure model was established in rabbits treated with doxorubicin, a Macrolide site chemotherapeutic agent with known dose-dependent cardiotoxicity, as previously described (19-21). The impact of NAC on myocardial apoptosis, NF- B activation and expression, Bcl-2 and Bax expression, oxidative pressure, inducible nitric oxide synthase (iNOS) expression and cardiac function was investigated. These studies will type the basis for additional MAO-A Gene ID evaluation with the therapeutic value of NAC in the treatment of heart failure. Materials and strategies Establishment of an in vivo heart failure model. A total of 50 Japanese white big-ear rabbits were purchased from the Experimental Animal Center of Medicine College of Wuhan University (Wuh.