In vitro cardiotoxicity and mechanism of action of the Egyptian green toad Bufo viridis skin secretions

Amphibian skin secretions are considered a rich source of biologically active compounds and are known to be rich in bufadienolides, peptides and alkaloids. Bufadienolides are cardioactive steroids derived from animals and plants as well. The current study was conducted to investigate the influence of skin secretions of the Egyptian green toad Bufo viridis (SSBV) on the cardiac electrical activity. Isolated toad’s heart was used to reveal the mechanism of action. Application of SSBV (40 μg/ml) into isolated toad’s heart significantly decreased the heart rate (HR) accompanied by an elongation in the conduction time (P–R interval). A pronounced increase of the ventricular contraction (R-wave amplitude) was observed after SSBV application. Marked electrocardiographic changes were induced within minutes (5–20 min) of SSBV perfusion of the isolated hearts; such as sinus arrhythmias, junctional ectopic beats, negative QRS deflection, ventricular tachycardia and heart block. The mechanism of action of SSBV was studied by direct application of different autonomic and ion channels antagonists (atropine sulphate, propranolol and verapamil) to isolated toad’s heart. Neither atropine nor verapamil could attenuate the noticed negative chronotropic and positive inotropic effects. Meanwhile, post-treatment with propranolol decreased R-wave amplitude. Taken together, it can be concluded that: (i) SSBV has a negative chronotropic, dromotropic and positive inotropic effects on isolated toad’s heart; (ii) the reported effects of SSBV could be due to inhibition of Na+–K+ ATPase and through ß-adrenergic receptors.