Acute hypoxia has been observed, different research have demonstrated that prolonged NF- B activation induces

Acute hypoxia has been observed, different research have demonstrated that prolonged NF- B activation induces myocardial injury (13,14). NF- B is usually a transcription element that regulates the expression of proinflammatory cytokines, such as interleukin (IL)-1, IL-6 and tumor necrosis factor- (TNF-), as well as genes associated with apoptosis (e.g. p53) (14). In a prior study in NF- B-null mice, enhanced cardiac function following myocardial infarction was observed (15). Oxidative strain may perhaps activate NF- B and initiate the transcription of many pro-apoptotic genes, including Bax, Fas and FasL, inducing myocardial cell apoptosis and advertising 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, Department of Cardiology,Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, Hubei 430071, P.R. China E-mail: [email protected] apoptosis, reactive oxygen speciesKey words: N-acetylcysteine, nuclear factor B, heart failure,WU et al: ROS, NF- B AND CARDIOMYOCYTE APOPTOSISscavenges ROS (16). Thus, in ischemia-reperfusion injury, NAC is in a position to prevent ROS-induced apoptosis (17), and in ischemic heart failure, NAC lowered superoxide anion levels and restored cardiomyocyte contractility (18). The present study aimed to decide the effect of NAC on oxidative stress, myocardial apoptosis and NF- B activation. An in vivo heart failure model was established in rabbits Brd Inhibitor review treated with doxorubicin, a chemotherapeutic agent with recognized dose-dependent cardiotoxicity, as previously described (19-21). The effect of NAC on myocardial apoptosis, NF- B activation and expression, Bcl-2 and Bax expression, oxidative stress, inducible nitric oxide COX-1 Inhibitor MedChemExpress synthase (iNOS) expression and cardiac function was investigated. These studies will type the basis for further analysis of the therapeutic worth of NAC in the remedy of heart failure. Components and techniques Establishment of an in vivo heart failure model. A total of 50 Japanese white big-ear rabbits have been purchased in the Experimental Animal Center of Medicine College of Wuhan University (Wuhan, China). Ten rabbits served as controls (control group). Heart failure was induced by doxorubicin within the remaining 40 rabbits utilizing previously described techniques (19,22). Briefly, doxorubicin hydrochloride (Zhejiang HiSun Minsheng Pharmaceutical Co., Ltd, Zhejiang, China) was diluted in normal saline at a concentration of 1 mg/ml and after that 1.0 mg/kg body weight was injected by means of the ear vein twice weekly for eight consecutive weeks. Heart failure was diagnosed by echocardiography with a sector scanning ultrasound probe at eight MHz (GE Vivid VII colour Doppler ultrasound, GE Medicals, Fairfield, CT, USA) in the finish of eight weeks. Of the 25 rabbits that developed heart failure, 13 (NAC group) received 300 mg/kg NAC (Hangzhou Minsheng Pharmaceutical Co., Ltd, Hangzhou, Zhejiang, China) after day-to-day for 4 weeks. The remaining 12 rabbits with heart failure (HF group) received normal saline of an equal volume. All of the animal experiments had been authorized by the Animal Care and Use Committee of Medicine College of Wuhan University. Echocardiography analysis. In all the three groups, echocardiography was performed in the finish of week 12 having a sector scanning u.