Protective effect of taurine on cardiotoxicity of the bufadienolides derived from toad ( Bufo bufo gargarizans Canto) venom in guinea-pigs in vivo and in vitro
Jiangsu Key laboratory for TCM formulae research, Nanjing University of Chinese Medicine, Nanjing, China.Toxicology mechanisms and methods (Impact Factor: 1.52). 01/2012; 22(1):1-8. DOI: 10.3109/15376516.2011.583295
In China, toad venom is an anti-inflammatory agent used in small doses for the treatment of various types of inflammation. Bufadienolides are cardioactive steroids responsible for the anti-inflammatory actions of toad venom. We studied the protective effect of taurine on the cardiotoxicity of bufadienolides in guinea-pigs. Bufadienolides (8 mg/kg) caused arrhythmias, cardiac dysfunction and death in guinea-pigs. Pretreatment with taurine (150, 300 mg/kg) significantly prevented bufadienolide-induced cardiotoxicity and reduced the mortality in vivo. Taurine markedly increased the cumulative doses of bufadienolides and resibufogenin required for lethal arrhythmia in ex vivo isolated guinea-pig heart. Taurine did not compromise the anti-inflammatory activity of the bufadienolides on concanavalin-A-stimulated proliferation of guinea-pig splenocytes in vitro. These data indicate that taurine can prevent bufadienolide-induced cardiotoxicity and could be a novel antidote in combination with bufadienolide therapy.
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ABSTRACT: Drug toxicity may occur due to dangerous drug combination. We aimed to investigate the influence of verapamil (a P-gp inhibitor) - bufadienolides interaction on cardiotoxicity and bufadienolide uptake by the isolated heart. The study was performed in Langendorff isolated perfused guinea-pig hearts by bufadienolides infusion in the absence and presence of verapamil (250, 500ng/ml). Arrhythmia parameters were evaluated by ECG and the content of bufadienolides in heart were measured by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS). In the present of verapamil, the wide QRS duration and lightly rapid heart rate (HR) were markedly reduced in the early stage of bufadienolide intoxication. However, the ECG changes characterized by prolonged P-R interval, and slow heart rate and low QRS amplitude in the late stage of bufadienolide intoxication were significantly enhanced. Furthermore, the contents of a variety of bufadienolide compounds in the verapamil+bufadienolide group were significantly higher when cardiac arrest occurred. Although verapamil reduced the bufadienolide-induced ventricular arrhythmias, verapamil worsened heart block and lethal bradycardia of bufadienolides partly via increasing the uptake of bufadienolides in heart tissue, which could compromise the protective effects of verapamil against bufadienolide intoxication. These results suggested that the verapamil may produce dangerous interactions with drugs containing bufadienolides.
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