Effects of N-acetylcysteine on skeletal muscle structure and function in a mouse model of peripheral arterial insufficiency

Author(s)

Roseguini, Bruno T. ^[1] ; Silva, Leonardo M. ^[1] ; Polotow, Tatiana G. ; Barros, Marcelo P. ; Souccar, Caden ^[2] ; Han, Sang W. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biophys, Escola Paulista Med, BR-04044010 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Pharmacol, Escola Paulista Med, Sect Nat Prod, BR-04044010 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF VASCULAR SURGERY; v. 61, n. 3, p. 777-786, MAR 2015.
• Web of Science Citations: 7

Abstract

Objective: Abnormalities in skeletal muscle structure and function are important contributors to exercise intolerance and functional decline in peripheral arterial disease. In this study, we tested the hypothesis that administration of N-acetylcysteine (NAC) would improve fatigue resistance and ameliorate the histopathological changes in skeletal muscle in a mouse model of peripheral arterial disease. We also anticipated that NAC treatment would lower the levels of biomarkers of oxidative damage in the ischemic muscle. Methods: Male Balb/c mice were subjected to bilateral ligation of the femoral artery and, after 2 weeks of recovery, received daily intraperitoneal injections of either NAC (150 mg/kg) or saline for 15 days. At the end of the treatment, the extensor digitorium longus (EDL) and soleus muscles were excised for assessment of contractile function in vitro and histological analysis. Free malondialdehyde and protein carbonyl levels were measured in the gastrocnemius muscle. Results: In the soleus muscle, force after 10 minutes of submaximal tetanic stimulation (60 Hz, 300 ms trains, 0.3 trains/s) was higher (P <.05) in NAC-treated animals (45% +/- 3% of the initial value; n = 7) when compared with controls (30.3% +/- 3%; n = 8). No differences were found in fatigue development between groups in the EDL muscle (ligated NAC, 35.7% +/- 1.9%; ligated saline, 37.5% +/- 1.1%). In addition, there was a tendency for lower levels of connective tissue deposition in the soleus of animals treated with NAC (n = 6) when compared with those that received only saline (n = 9) (ligated NAC, 16% +/- 2% vs ligated saline, 24% +/- 2%; P = .057). No differences were found in lipid peroxidation or protein carbonyl levels between ligated saline and ligated NAC groups. Conclusions: Taken together, these results indicate that treatment with NAC improves fatigue resistance in the soleus but not the EDL muscle in a model of peripheral arterial insufficiency. (AU)

• FAPESP's process: 11/00859-6 - Role of GM-CSF in the repair of muscule injury: gene therapy for muscle injuries
• Grantee: Sang Won Han
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/51344-3 - Presynaptic mechanisms involved in the cholinergic and GABAergic transmitter release in the central nervous system of the mdx mouse: analysis of nicotinic modulation in young and adult mice
• Grantee: Caden Souccar
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/18197-0 - Exercise as a tool to enhance the efficacy of mesenchymal cell therapy in a model of peripheral arterial disease
• Grantee: Bruno Tesini Roseguini
• Support Opportunities: Scholarships in Brazil - Post-Doctoral