Cardiotoxicity and neurotoxicity features of Aconiti Radix ethanol extract and its impacts on vascular endothelial / 中草药

ABSTRACT

Objective: To investigate the features of cardiotoxicity and neurotoxicity and the influence on vascular endothelial of ethanol extract of Aconiti Radix (AR). Methods: Totally 45 Wistar rats were randomly divided into four groups, and ig given low-, middle-, and high-dose 70% ethanol extract of AR (in the raw drug dose of 2.5, 5.0, and 7.5 g/kg respectively) for 15 d. The toxic reaction and death condition were observed during administration. The electrocardiogram (ECG) change was tested after administration. Blood was collected for blood routine and blood biochemistry analysis. Brain was harvested for calculating viscera index and pathological examination. Left ventricular and hippocampus were extracted and stained with electron microscope (EM) methods. Results: At the end of treatment, all rats were sacrificed in the high-dose AR group. The mortality and hematologic parameters including RBC, HGB, HCT, ALT, UREA, and GLU were significantly increased in the middle-dose AR groups compared with control group. Arrhythmia especially ventricular arrhythmia occurred in low- and middle-dose AR group. Brain index and number of pyknotic neurons in focal area of hippocampus were significantly increased in middle-dose AR group. EM examination indicated that dissolution of neuronal inclusions, nuclear fragmentation, and coagulation necrosis of glial cells were prominent in the hippocampus tissue in middle-dose AR group. In the middle-dose AR group, the vascular endothelial cells injury and apoptosis were obviously observed in left ventricular and hippocampus separately. Conclusion: The ethanol extract of AR can lead to cardiotoxicity and neurotoxicity especially vascular endothelial injury in dose-dependent manner.