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Influence of N-acetylcysteine on apoptosis signaling in skeletal muscle of rats with chronic heart failure

Grant number: 12/07149-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2012
Effective date (End): February 28, 2013
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Marina Politi Okoshi
Grantee:Paula Felippe Martinez
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

There are few studies evaluating mechanisms involved in skeletal muscle fibers apoptosis during heart failure (HF). Oxidative stress has a well-established role in apoptosis intracellular signaling pathways. Previous works have shown a link between glutathione and apoptosis; however, this relationship has not been defined in skeletal muscle during HF. N-acetylcysteine (NAC) is an important source of cysteine for glutathione synthesis. NAC administration restored total glutathione levels and decreased oxidative stress markers in myocardium of infarcted rats. The aim of this study is to verify whether NAC administration normalizes total levels and redox status of glutathione and inhibits or attenuates apoptosis signaling pathways in skeletal muscle of rats with myocardial infarction (MI)-induced HF. Wistar rats will be assorted in three groups: Sham, MI-C (without treatment), and MI-NAC (treated with NAC for two months). Gastrocnemius muscle will be analyzed six months after MI induction. Ventricular dysfunction and HF will be confirmed by echocardiography and pathologic features, respectively. Antioxidant enzymes activity will be evaluated by spectrophotometry. Total generation of reactive oxygen species will be assessed by quantification of dihydroethidium oxidation-derived products by HPLC. Muscular glutathione levels, TNF-alpha serum concentration, and DNA fragmentation will be analyzed by available commercial kits. Expression of proteins involved in apoptosis signaling pathways will be quantified by Western blot. Myosin heavy chain isoforms will be evaluated by polyacrylamide gel electrophoresis. Statistical analysis: ANOVA and Bonferroni.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MARTINEZ, PAULA F.; BONOMO, CAMILA; GUIZONI, DANIELE M.; OLIVEIRA JUNIOR, SILVIO A.; DAMATTO, RICARDO L.; CEZAR, MARCELO D. M.; LIMA, ALINE R. R.; PAGAN, LUANA U.; SEIVA, FABIO R.; BUENO, RENATA T.; FERNANDES, DENISE C.; LAURINDO, FRANCISCO R.; ZORNOFF, LEONARDO A. M.; OKOSHI, KATASHI; OKOSHI, MARINA P. Modulation of MAPK and NF-kappa B Signaling Pathways by Antioxidant Therapy in Skeletal Muscle of Heart Failure Rats. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v. 39, n. 1, p. 371-384, 2016. Web of Science Citations: 13.

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