Andrographolide protects against isoproterenol-induced myocardial infarction in rats through inhibition of L-type Ca2+ and increase of cardiac transient outward K+ currents

Author(s):Show less -

Elasoru, Seyi Elijah ^[1] ; Rhana, Paula ^[1] ; de Oliveira Barreto, Tatiane ^[1] ; de Souza, Dayane Lorena Naves ^[1] ; Menezes-Filho, Jose Evaldo Rodrigues ^[1] ; Souza, Diego Santos ^[2] ; Moreira, Matheus Vilardo Loes ^[3] ; Campos, Marco Tulio Gomes ^[3] ; Adedosu, Olaniyi Temitope ^[4] ; Roman-Campos, Danilo ^[2] ; Melo, Marilia Martins ^[3] ; Cruz, Jader Santos ^[1]

Affiliation

^[1] Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, Belo Horizonte, MG - Brazil

^[2] Univ Fed Sao Paulo, Paulista Sch Med, Dept Biophys, Sao Paulo - Brazil

^[3] Univ Fed Minas Gerais, Sch Vet, Dept Clin & Vet Surg, Belo Horizonte, MG - Brazil

^[4] Ladoke Akintola Univ Technol, Dept Biochem, Ogbomosho - Nigeria

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 906, SEP 5 2021.
• Web of Science Citations: 0

Abstract

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 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. After all treatments, cardiac-specific parameters that define cardiac health and early subacute MI were measured in all groups using both biophysical and pharmacological assay methods. Isoproterenol administration significantly (P < 0.05) increased cardiac mass indexes, systemic cardiac biomarkers, infarct size and caused cardiac histological alterations; significantly (P < 0.05) increased heart rate, QRS \& QTc intervals and caused ST-segment elevation; significantly (P < 0.05) increased myocytes shortening, action potential duration (APD), L-type Ca2+ current (ICa,L) density and significantly (P < 0.05) decreased transient outward K+ current (Ito) density typical of the early subacute MI. Interestingly, pretreatment with andrographolide prevented and or minimized these anomalies, notably, by reducing ICa,L density and increasing Ito density significantly. Therefore, andrographolide could be seen as a promising therapeutic agent capable of making the heart resistant to early subacute infarction and it could be used as template for the development of semisynthetic drug(s) for cardiac protection against MI. (AU)

• FAPESP's process: 19/21304-4 - Arrhythmogenic mechanisms in right heart diseases
• Grantee: Danilo Roman Campos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/18918-0 - Role of nitric oxide in cardiac arrhythmias during Hypothyroidism
• Grantee: Diego Santos de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral