Modulation of MAPK and NF-κB Signaling Pathways by Antioxidant Therapy in Skeletal Muscle of Heart Failure Rats

• Main Authors: Paula F. Martinez, Camila Bonomo, Daniele M. Guizoni, Silvio A. Oliveira Junior, Ricardo L. Damatto, Marcelo D.M. Cezar, Aline R.R. Lima, Luana U. Pagan, Fabio R. Seiva, Renata T. Bueno, Denise C. Fernandes, Francisco R. Laurindo, Leonardo A.M. Zornoff, Katashi Okoshi, Marina P. Okoshi
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2016-06-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Oxidative stress; Intracellular signaling; Myocardial infarction; Cardiac failure; Skeletal muscle; Myopathy
• Online Access: http://www.karger.com/Article/FullText/445631
• ISSN: 1015-8987; 1421-9778

Background/Aims: Although increased oxidative stress plays a role in heart failure (HF)-induced skeletal myopathy, signaling pathways involved in muscle changes and the role of antioxidant agents have been poorly addressed. We evaluated the effects of N-acetylcysteine (NAC) on intracellular signaling pathways potentially modulated by oxidative stress in soleus muscle from HF rats. Methods and Results: Four months after surgery, rats were assigned to Sham, myocardial infarction (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. Oxidative stress was evaluated in serum and soleus muscle; malondialdehyde was higher in MI-C than Sham and did not differ between MI-C and MI-NAC. Oxidized glutathione concentration in soleus muscle was similar in Sham and MI-C, and lower in MI-NAC than MI-C (Sham 0.168 ± 0.056; MI-C 0.223 ± 0.073; MI-NAC 0.136 ± 0.023 nmol/mg tissue; p = 0.014). Western blot showed increased p-JNK and decreased p38, ERK1/2, and p-ERK1/2 in infarcted rats. NAC restored ERK1/2. NF-κB p65 subunit was reduced; p-Ser276 in p65 and IκB was increased; and p-Ser536 unchanged in MI-C compared to Sham. NAC did not modify NF-κB p65 subunit, but decreased p-Ser276 and p-Ser536. Conclusion: N-acetylcysteine modulates MAPK and NF-κB signaling pathways in soleus muscle of HF rats.