Eugenol interacts with cardiac sodium channel and reduces heart excitability and arrhythmias

Autor(es)

Teixeira-Fonseca, Jorge Lucas ^{[1, 2]} ; Santos-Miranda, Artur ^[2] ; da Silva, Joab Barbosa ^[1] ; Marques, Leisiane Pereira ^{[1, 2]} ; Joviano-Santos, Julliane Vasconcelos ^[2] ; Chaves Nunes, Paula Idma ^[1] ; Roman-Campos, Danilo ^[2] ; Santana Gondim, Antonio Nei ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Estado Bahia UNEB, Lab Biofis & Farmacol Coracao, Dept Educ Campus 12, Guanambi, BA - Brazil

^[2] Univ Fed Sao Paulo UNIFESP, Dept Biofis, Lab Cardiobiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 282, OCT 1 2021.
• Citações Web of Science: 0

Resumo

Aims: Eugenol is a natural compound found in the essential oils of many aromatic plants. The compound is used as a local anesthetic because of its inhibitory effect on the voltage-gated Na+ channels (Na-v), which are expressed in the nociceptive neurons. Eugenol has shown wide range of activities in the cardiovascular system; most of these activities are attributed to the modulation of voltage-sensitive Ca2+ channels. However, its action on Na(v)1.5, the main subtype of Na-v expressed in the mammalian myocardium, is unknown. The interaction of eugenol with Na(v)1.5 could also contribute to its antiarrhythmic properties in vitro and ex vivo. We investigated the compound's effect on sodium current (I-Na) and its possible cardiac antiarrhythmic activity. Methods: The effect of eugenol on cardiac contractility was investigated using isolated atrium from guinea pig (for isometric force measurements). The compound's effect on I-Na was evaluated using human embryonic cell transiently expressing human Na(v)1.5 and patch-clamp technique. Key findings: Eugenol caused negative inotropic and chronotropic effects in the atria. In the ex vivo arrhythmia model, eugenol decreased atrial pacing disturbance induced by ouabain. Eugenol reduced the I-Na in a concentration-dependent manner. Furthermore, the compound left-shifted the stationary inactivation curve, delayed recovery from inactivation of the I-Na, and preferentially blocked the channel in the inactivated state. Importantly, eugenol was able to attenuate the late sodium current. All these aspects are considered to be antiarrhythmic. Significance: Overall, our findings demonstrate that eugenol has antiarrhythmic activity due, at least in part, to its interaction with Na(v)1.5. (AU)

• Processo FAPESP: 18/22830-9 - Envolvimento do eixo de sinalização da proteína cinase II dependente de Ca2+-calmodulina (CaMKII) nas alterações elétricas e contráteis na fase crônica da doença de Chagas em modelo murino
• Beneficiário: Artur Santos Miranda
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/20777-3 - Variantes genéticas do canal para sódio Nav 1.5 e suas consequências terapêuticas
• Beneficiário: Julliane Vasconcelos Joviano dos Santos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/21304-4 - Mecanismos arritmogênicos em doenças do coração direito
• Beneficiário: Danilo Roman Campos
• Modalidade de apoio: Auxílio à Pesquisa - Regular