title: N-acetylcysteine reduces oxidative stress, nuclear factor‑κB activity and cardiomyocyte apoptosis in heart failure.
abstract: The roles of oxidative stress on nuclear factor (NF)‑κB activity and cardiomyocyte apoptosis during heart failure were examined using the antioxidant N‑acetylcysteine (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, apoptosis‑related protein expression, NF‑κBp65 expression and activity, total anti‑oxidative capacity (tAOC), 8‑iso‑prostaglandin F2α (8‑iso‑PGF2α) expression and glutathione (GSH) expression levels were determined. In the HF group, reduced tAOC, GSH levels and Bcl‑2/Bax ratios as well as increased 8‑iso‑PGF2α levels and apoptosis were observed (all P<0.05), which were effects that were attenuated by the treatment with NAC. NF‑κBp65 and iNOS levels were significantly higher and the P‑IκB‑α levels were significantly lower in the HF group; expression of all three proteins returned to pre‑HF levels following treatment with NAC. Myocardial cell apoptosis was positively correlated with left ventricular end-diastolic pressure (LVEDP), NF‑κBp65 expression and 8‑iso‑PGF2α levels, but negatively correlated with the maximal and minimal rates of increase in left ventricular pressure (+dp/dtmax and ‑dp/dtmin, respectively) and the Bcl‑2/Bax ratio (all P<0.001). The 8‑iso‑PGF2α 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 NF‑κB activation and reduced myocardial cell apoptosis in an in vivo heart failure model.
authors.affiliation: Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wu
authors.affiliation: Hanyang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: An-Yu
authors.initials: AY
authors.lastname: Luo
authors.affiliation: Department of Pharmacology and Toxicology, Wright State University, Dayton, OH, USA.
authors.forename: Yi-Rong
authors.initials: YR
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Jiang-Hua
authors.initials: JH
authors.lastname: Ren
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D005978:Glutathione / Q000032:analysis; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics; D020672:I-kappa B Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D000072000:NF-KappaB Inhibitor alpha; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011817:Rabbits; D051996:Transcription Factor RelA / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; D000072000:NF-KappaB Inhibitor alpha; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D005978:Glutathione; D000111:Acetylcysteine