Influence of metformin in cardiac remodeling of rats exposed to cigarette smoke

• Grant number: 16/25676-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2017
• Effective date (End): October 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Paula Schmidt Azevedo Gaiolla
• Grantee: Letícia Dalla Vecchia Grassi
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Smoking is a frequent habit in the world's population and it is considered the leading cause of preventable mortality. Smoking increases twice the risk of death from cardiovascular disease. Cigarette smoke is toxic to the myocardium, which can cause cardiac remodeling and the development of heart failure. The mechanisms of cardiac remodeling induced by the toxicity of cigarette smoke are poorly understood. Among them is the alteration of cardiac energy metabolism. Another possible factor is the appearance of peripheral insulin resistance, however the pathways of glucose metabolism and the role of insulin resistance in the heart of smokers have not been clarified yet. Consequently, it is necessary to study the routes of toxicity induced by cigarette smoke and its direct action on the myocardium. As metformin is a drug that acts on insulin resistance, it was chosen to assist in the evaluation of the participation of cardiac metabolism in smoking-induced cardiomyopathy. The aim of the study is to evaluate the role of metformin in cardiac remodeling induced by exposure to cigarette smoke and to study the mechanisms by which cardiac injury is established. For this purpose, 60 Wistar rats divided into 4 groups will be used: control group C (n = 15); MET group (n = 15) - animals with metformin ingestion diluted in water; EFC group (n = 15) - animals exposed to cigarette smoke; EFC-MET (n = 15) - animals exposed to cigarette smoke and with ingestion of metformin diluted in water. The animals will be submitted to 2 months of observation followed by euthanasia. They will be studied by echocardiographic evaluation; Biochemical dosages for enzymes of cardiac energy metabolism; Western blot analysis for the SIRT-1 Akt-1 and phosphorylated Akt proteins, AMPK, GLUT-4 and HOMA Index for analysis of insulin resistance. (AU)

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)

AZEVEDO, PAULA SCHMIDT; POLEGATO, BERTHA F.; PAIVA, SERGIO; COSTA, NARA; SANTOS, PRISCILA; BAZAN, SILMEIA; HENRIQUE FERNANDES, ANA ANGELICA; FABRO, ALEXANDRE; PIRES, VANESSA; TANNI, SUZANA E.; et al. The role of glucose metabolism and insulin resistance in cardiac remodelling induced by cigarette smoke exposure. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, v. 25, n. 2, DEC 2020. (14/24197-0, 16/14547-0, 16/25676-5)