The novel antidote Bezoar Bovis prevents the cardiotoxicity of Toad (Bufo bufo gargarizans Canto) Venom in mice

Abstract

Toad Venom, called chansu (CS) in China, is an anti-inflammatory drug used in small doses for the treatment of various types of inflammation in China. Its use is hampered by the cardiotoxicity of bufadienolides derived from Toad Venom. Bezoar Bovis is another frequently used drug in Toad Venom preparations for the treatment of inflammatory or cardiovascular diseases in Asia. We explored whether Bezoar Bovis could protect against CS-induced acute toxicity in mice. Toxicity was assessed by the general features of poisoning, electrocardiography (ECG), and levels of creatine kinase (CK), lactate dehydrogenase (LDH) and calcium ions (Ca(2+)) in cardiac tissues. Toad Venom (90 mg/kg) caused opisthotonus, ventricular arrhythmias, and increases in cardiac levels of Ca(2+), CK and LDH. Pretreatment with Bezoar Bovis (120, 240 and 480 mg/kg) significantly reduced the prevalence of opisthotonus and mortality, and prevented cardiotoxicity in CS-treated mice as evidenced by decreases in the scores of arrhythmias and cardiac levels of CK, LDH and Ca(2+). Furthermore, the bilirubin, and taurine derived from Bezoar Bovis offered marked protection against the arrhythmias induced by CS or bufalin in vivo and in vitro. An anti-inflammatory study showed that Bezoar Bovis did not compromise the anti-inflammatory activity of Toad Venom on concanavalin-A (ConA)-stimulated proliferation of human peripheral blood mononuclear cells. These results suggested that Bezoar Bovis elicited protective and anti-arrhythmic effects against Toad Venom intoxication in mice, and is a novel antidote in combination with Toad Venom therapy.