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

Teixeira‐Fonseca, Jorge Lucas; Santos‐Miranda, Artur; Silva, Joab Barbosa da; Marques, Leisiane Pereira; Joviano‐Santos, Julliane V.; Nunes, Paula Idma Chaves; Roman‐Campos, Danilo; Gondim, Antônio Nei Santana

doi:10.1016/j.lfs.2021.119761

Cited by 14 publications

(11 citation statements)

References 28 publications

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“…The RA was cut perpendicularly and mounted in a tank for isolated organs containing Tyrode's solution (mM): 140 NaCl, 5.4 KCl, 1.8 CaCl 2 , 1.0 MgCl 2 , 0.33 NaH 2 PO 4 , 11 Dextrose and 5 HEPES continuously gasified with 99.9% O 2 . 20 The ends of the RA were suspended horizontally by stainless steel hooks and equilibrated under a resting tension of 0.5 gf (4.9 mN) for at least 40 min before being challenged with increasing concentration of ranolazine (SIGMA Chemical Co. St. Louis, MO, USA). The stock solution of the drug was prepared in DMSO and subsequently diluted with Tyrode's solution.…”

Section: Right Atrium Preparationmentioning

confidence: 99%

Ranolazine exerts atrial antiarrhythmic effects in a rat model of monocrotaline‐induced pulmonary hypertension

Teixeira‐Fonseca

Conceição

Leal‐Silva

et al. 2023

Basic Clin Pharma Tox

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Atrial arrhythmias are a hallmark of heart diseases. The antiarrhythmic drug ranolazine with multichannel blocker properties is a promising agent to treat atrial arrhythmias. We therefore used the rat model of monocrotaline-induced pulmonary-hypertension to assess whether ranolazine can reduce the incidence of ex vivo atrial arrhythmias in isolated right atrium. Four-week-old Wistar rats were injected with 50 mg/kg of monocrotaline, and isolated right atrium function was studied 14 days later. The heart developed right atrium and right ventricular hypertrophy, and the ECG showed an increased P wave duration and QT interval, which are markers of the disease. Moreover, monocrotaline injection caused enhanced chronotropism and faster kinetics of contraction and relaxation in isolated right atrium. Additionally, in a concentration-dependent manner, ranolazine showed chronotropic and ionotropic effects upon isolated right atrium, with higher potency in the control when compared with experimental model. Using a burst pacing protocol, the isolated right atrium from the monocrotaline-treated animals was more susceptible to develop arrhythmias, and ranolazine was able to attenuate the phenotype. Thus, we concluded that the rat model of monocrotaline-induced pulmonary-hypertension develops right atrium remodelling, which increased the susceptibility to present ex vivo atrial arrhythmias, and the antiarrhythmic drug ranolazine ameliorated the phenotype.

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Section: Right Atrium Preparationmentioning

confidence: 99%

Ranolazine exerts atrial antiarrhythmic effects in a rat model of monocrotaline‐induced pulmonary hypertension

Teixeira‐Fonseca

Conceição

Leal‐Silva

et al. 2023

Basic Clin Pharma Tox

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“…11,17 As a non-specific channel blocker, in addition to its ability to block Ca 2+ current, eugenol is able to reduce I Na studied in heterologous expression system using the cardiac isoform of the human sodium channel expressed in HEK cells. 7 Therefore, we decided to investigate the effects of the compound on the electrophysiological properties of I Na from guinea pig-derived cardiomyocytes, given that heterologous expression of ion channels may not fully represent the pharmacological properties of antiarrhythmic drugs. 8,9 In isolated hearts, eugenol delayed the onset of arrhythmias and the time required to induce ventricular fibrillation, as measured in the ECG.…”

Section: Discussionmentioning

confidence: 99%

“…23 In a previous investigation, it was found that eugenol is able to block the I Na,Late observed in the human Na V 1.5 carrying the pathogenic mutation ΔKPQ. 7 Thus, some of the antiarrhythmic effect attributed to eugenol in guinea pig hearts exposed to the compound could be due to the blockage of I Na,Late .…”

Section: Discussionmentioning

confidence: 99%

“…6 Using human embryonic kidney cells transiently expressing human Na V 1.5, it was shown that eugenol reduced the I Na in a concentration-dependent manner, and also decreased the late component of I Na (I Na,Late ), which shows significant arrhythmic properties. 7 Despite the benefit of heterologous expression system, it does not represent full extent of the pharmacological profile of antiarrhythmic drugs. 8,9 In mammalian ventricular myocardium eugenol reduces the isometric force developed by the papillary muscles possibly due to the blockade of L-type Ca 2+ current (I Ca,L ).…”

Section: Introductionmentioning

confidence: 99%

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Eugenol delays the onset of ouabain‐induced ventricular cardiac arrhythmias in guinea pigs

Teixeira‐Fonseca,

Santos‐Miranda,

Marques

et al. 2023

Basic Clin Pharma Tox

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Eugenol is an aromatic compound used in the manufacture of medicines, perfumes, cosmetics and as an anesthetic due to the ability of the drug to block the neuronal isoform of voltage‐gated Na+ channels (NaV). Some arrhythmias are associated with gain of function in the peak sodium current (INa) found in cardiomyocytes, and antiarrhythmic sodium channel blockers are commonly used in the clinical practice. This study sought to elucidate the potential mechanisms of eugenol’s protection in the arrhythmic model of ouabain‐induced arrhythmias in guinea pig heart. Ex vivo arrhythmias were induced using 50 μmol.l−1 of ouabain. The antiarrhythmic properties of eugenol were evaluated in the ex vivo heart preparation and isolated ventricular cardiomyocytes. The compound’s effects on cardiac sodium current and action potential using the patch‐clamp technique were evaluated. In all, eugenol decreased the ex vivo cardiac arrhythmias induced by ouabain. Furthermore, eugenol showed concentration dependent effect upon INa, left‐shifted the stationary inactivation curve and delayed the recovery from inactivation of the sodium current. All these aspects are considered to be antiarrhythmic. Our findings demonstrate that eugenol has antiarrhythmic activity, which may be partially explained by the ability of eugenol to change de biophysical properties of INa of cardiomyocytes.

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“…The RA was cut perpendicularly and mounted in a tank for isolated organs containing Tyrode's solution (mM): 140 NaCl, 5.4 KCl, 1.8 CaCl 2 , 1.0 MgCl 2 , 0.33 NaH 2 PO 4 , 11 dextrose and 5 HEPES continuously gasified with 99.9% O 2. 14 The ends of the RA were suspended horizontally by stainless steel hooks and equilibrated under a resting tension of 0.5 gf (4.9 mN) for at least 40 min before being challenged with amiodarone or applying the bursting pacing protocol (SIGMA Chemical). The vehicle at the maximum concentration did not cause any acute effect in the isolated RA.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of right atrium structure and function in a rat model of monocrotaline‐induced pulmonary hypertension: Exploring the possible antiarrhythmic properties of amiodarone

Teixeira‐Fonseca,

Joviano‐Santos,

da Silva Alcântara

et al. 2023

Clin Exp Pharma Physio

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Atrial arrhythmias (AA) are common in pulmonary hypertension (PH) and are closely associated with poor clinical outcomes. One of the most studied models to investigate PH is the rat model of monocrotaline (MCT) induced PH (MCT‐PH). To date, little is known about right atrium (RA) function in the MCT‐PH model and the propensity of RA to develop arrhythmias. Therefore, the aim of the study was to evaluate the function of the RA of control (CTRL) and MCT treated rats, and the ability of amiodarone, a classical antiarrhythmic, to prevent the occurrence of AA in the RA in MCT‐PH rats. RA function was studied in MCT‐PH rats 20 days after a single subcutaneous injection of MCT 50 mg/kg. The histological results indicated the presence of RA and right ventricular hypertrophy. Surface electrocardiogram demonstrated increased P wave duration, PR wave duration and QT interval in MCT rats. RA from MCT rats were more susceptible to develop ex vivo burst pacing arrhythmias when compared to CTRL. Intriguingly, amiodarone in clinical relevant concentration was not able to prevent the occurrence arrhythmias in RA from MCT‐PH animals. Hence, we conclude that the rat model of MCT‐PH impairs RA structure and function, and acute exposure of RA to amiodarone in clinical relevant concentration is not able to attenuate the onset of arrhythmias in the ex vivo RA preparation.

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

Cited by 14 publications

References 28 publications

Ranolazine exerts atrial antiarrhythmic effects in a rat model of monocrotaline‐induced pulmonary hypertension

Ranolazine exerts atrial antiarrhythmic effects in a rat model of monocrotaline‐induced pulmonary hypertension

Eugenol delays the onset of ouabain‐induced ventricular cardiac arrhythmias in guinea pigs

Evaluation of right atrium structure and function in a rat model of monocrotaline‐induced pulmonary hypertension: Exploring the possible antiarrhythmic properties of amiodarone

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