Cholinergic Stimulation Improves Oxidative Stress and Inflammation in Experimental Myocardial Infarction

• Published in: Scientific reports Vol. 7; no. 1; pp. 13687 - 12
• Main Authors: Bezerra, Otávio C., França, Cristiane Miranda, Rocha, Juraci Aparecida, Neves, Gizele A., Souza, Pamella Ramona M., Teixeira Gomes, Mariana, Malfitano, Christiane, Loleiro, Tatiane C. Alba, Dourado, Paulo Magno, Llesuy, Susana, de Angelis, Katia, Irigoyen, Maria Claudia C., Ulloa, Luis, Consolim-Colombo, Fernanda M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.10.2017; Nature Publishing Group
• Subjects: 13/21; 13/51; 631/250/127/1213; 692/308/1426; 692/4019/592/2725; 692/4019/592/75/230; 82/80; 96/63; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antioxidants - pharmacology; Blood pressure; Carbonyl compounds; Cardiotonic Agents - pharmacology; Catalase; Cholinesterase Inhibitors - pharmacology; Coronary artery; Cytokines; Cytokines - metabolism; Disease Models, Animal; Enzymatic activity; Foxp3 protein; Glutathione peroxidase; Heart attacks; Heart rate; Hemodynamics - drug effects; Humanities and Social Sciences; Immunohistochemistry; Immunomodulation; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Interleukin 10; Interleukin 6; Lipid peroxidation; Lymphocytes; Lymphocytes T; Macrophages; Male; multidisciplinary; Myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Neuromodulation; Ostomy; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Oxidizing agents; Parasympathetic nervous system; Peroxidation; Pyridostigmine Bromide - pharmacology; Random Allocation; Rats, Wistar; Rodents; Science; Science (multidisciplinary); Superoxide dismutase; Surgery
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-14021-8

We previously reported that cholinergic stimulation with pyridostigmine (PY) induces anti-inflammatory cell recruitment soon after myocardial infarction (MI). In this study, we evaluated the anti-inflammatory effects of PY during the proliferative phase of cardiac repair by analyzing the infiltration of macrophages, Treg lymphocytes, oxidative stress and inflammatory cytokines. Wistar rats underwent control sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated (untreated infarcted group, I) or to receive PY (30 mg·kg(−1)·day(−1)) in the supplied water (infarcted treated group, I + PY). Blood pressure and heart rate variability were registered at day 5 post-MI. The animals were euthanized 7 days after thoracotomy, when the hearts were removed and processed for immunohistochemistry (CD68, CD206, FOXP3), cytokines (IL-1β, IL-6, IL-10, TNF-α) and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, lipidic and protein peroxidation). PY treatment increased parasympathetic modulation, M2 macrophages and the anti-oxidant enzyme activity but reduced protein oxidation (carbonyls) and the concentration of IL-1β, IL-6, TNF-α and IL-10. Cholinergic stimulation induces parasympathetic neuro-immune modulation and anti-inflammatory cell enrollment as well as prevents oxidative stress and cytokine production after MI.