title: Influence of N- acetylcysteine on oxidative stress in slow-twitch soleus muscle of heart failure rats.
abstract: BACKGROUND
  Chronic heart failure is characterized by decreased exercise capacity with early exacerbation of fatigue and dyspnea. Intrinsic skeletal muscle abnormalities can play a role in exercise intolerance. Causal or contributing factors responsible for muscle alterations have not been completely defined. This study evaluated skeletal muscle oxidative stress and NADPH oxidase activity in rats with myocardial infarction (MI) induced heart failure.
  
  
  RESULTS
  Four months after MI, rats were assigned to Sham, MI-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. In soleus muscle, glutathione peroxidase and superoxide dismutase activity was decreased in MI-C and unchanged by NAC. 3-nitrotyrosine was similar in MI-C and Sham, and lower in MI-NAC than MI-C. Total reactive oxygen species (ROS) production was assessed by HPLC analysis of dihydroethidium (DHE) oxidation fluorescent products. The 2-hydroxyethidium (EOH)/DHE ratio did not differ between Sham and MI-C and was higher in MI-NAC. The ethidium/DHE ratio was higher in MI-C than Sham and unchanged by NAC. NADPH oxidase activity was similar in Sham and MI-C and lower in MI-NAC. Gene expression of p47(phox) was lower in MI-C than Sham. NAC decreased NOX4 and p22(phox) expression.
  
  
  CONCLUSIONS
  We corroborate the case that oxidative stress is increased in skeletal muscle of heart failure rats and show for the first time that oxidative stress is not related to increased NADPH oxidase activity.
authors.affiliation: Botucatu Medical School, UNESP, Botucatu, Brazil.
authors.forename: Paula F
authors.initials: PF
authors.lastname: Martinez
authors.forename: Camila
authors.initials: C
authors.lastname: Bonomo
authors.forename: Daniele M
authors.initials: DM
authors.lastname: Guizoni
authors.forename: Silvio A Oliveira
authors.initials: SA
authors.lastname: Junior
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Damatto
authors.forename: Marcelo D M
authors.initials: MD
authors.lastname: Cezar
authors.forename: Aline R R
authors.initials: AR
authors.lastname: Lima
authors.forename: Luana U
authors.initials: LU
authors.lastname: Pagan
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Seiva
authors.forename: Denise C
authors.initials: DC
authors.lastname: Fernandes
authors.forename: Francisco R M
authors.initials: FR
authors.lastname: Laurindo
authors.forename: Ethel L B
authors.initials: EL
authors.lastname: Novelli
authors.forename: Luiz S
authors.initials: LS
authors.lastname: Matsubara
authors.forename: Leonardo A M
authors.initials: LA
authors.lastname: Zornoff
authors.forename: Katashi
authors.initials: K
authors.lastname: Okoshi
authors.forename: Marina P
authors.initials: MP
authors.lastname: Okoshi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D004996:Ethidium / Q000031:analogs & derivatives / Q000032:analysis; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006333:Heart Failure / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D006352:Heart Ventricles / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: C506392:2-hydroxyethidium; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C067883:dihydroethidium; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C515768:Cyba protein, rat; C060505:neutrophil cytosolic factor 1; D004996:Ethidium; D000111:Acetylcysteine