Biophysical and pharmacological evaluation of protective potentials of andrographolide against isoproterenol-induced myocardial infarction in rats

• Autor(a) principal: Seyi Elijah Elasoru
• Data de Publicação: 2021
• Tipo de documento: Tese
• Idioma: eng
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: http://hdl.handle.net/1843/36391; https://orcid.org/0000-0002-2111-239X
• topic: Myocardial infarction; Andrographolide; Cardiac protection; Calcium current; Potassium current; Bioquímica e imunologia; Infarto do miocárdio; Andrographis

Myocardial infarction (MI) is the irreversible injury of the myocardium caused by prolonged myocardial ischemia and is a major cause of heart failure and eventual death among ischemic patients. The current trend of mortality due to MI and shortcomings of available therapeutics informed the need for an alternative remedy that could make the heart more resistant to infarction. Andrographolide is the principal compound in Andrographis paniculata, an indigenous plant commonly included in herbal concoction indicated for cardiovascular diseases and chest pains. Therefore, the present study assessed the protective potentials of andrographolide against isoproterenol-induced myocardial infarction in rats. Animals were randomly divided into four groups: Control (Ctr) group received 0.9 % saline solution once daily for 21 days, Isoproterenol (Iso) group received 0.9 % saline solution once daily for 19 days followed by 80 mg/kg/day of isoproterenol hydrochloride solution on day 20 and 21, Andrographolide (Andro) group received 20 mg/kg/day of andrographolide for 21 days, and Andrographolide plus Isoproterenol (Andro + Iso) group received 20 mg/kg/day of andrographolide for 21 days with co-administration of 80 mg/kg/day of isoproterenol hydrochloride solution on day 20 and 21. At the end of all treatments, cardiac-specific parameters that define cardiac health and MI were evaluated in all groups. Likewise, the mechanical and electrical profiles that shapes the functions of the heart were assessed in cardiomyocytes isolated from each group using standard assay methods. In addition, effects of Andro on these mechanical and electrical profiles were further substantiated with in-vitro tests and compared to standard drug of MI. Iso caused: ST-segment elevation and significant (p<0.05) increases in heart rate, QRS, QT & QTc interval; significant (p<0.05) increases in cardiac mass indexes; significant (p<0.05) increases in systemic troponin I (cTnI), creatine kinase (CK), creatine kinase-MB fraction (CK-MB), aspartate transaminase (AST) & leukocyte levels; significant (p<0.05) increase of infarct size; cardiac histological alterations; significant (p<0.05) increases in myocytes shortening, maximal velocity of contraction (+dL/dt) & maximal velocity of relaxation (-dL/dt); significant (p<0.05) prolongation of action potential duration (APD); significant (p<0.05) increase in L-type calcium current (ICa,L) density and significant (p<0.05) decrease in transient outward potassium current (Ito) density typical of the onset of MI. Interestingly, pretreatment with Andro prevented and / or minimized these anomalies, notably, by reducing myocyte shortening, +dL/dt, -dL/dt, APD, ICa,L density and increasing Ito density significantly (p<0.05). Furthermore, in-vitro results supported the in-vivo effects of Andro on myocyte shortening, +dL/dt, -dL/dt, APD, ICa,L density, and Ito density and indicated that the effects are concentration-dependent. Therefore, andrographolide could be seen as a promising therapeutic agent capable of making the heart resistant to infarction and it could be used as template for the development of semisynthetic drug(s) for cardiac protection against MI.