Antagonistic Effects of Tetrodotoxin on Aconitine-induced Cardiac Toxicity
| Autor: | Makiko Hayashida, Youkichi Ohno, Akito Tezuka, Takiyoshi Ono, Hideyuki Hayakawa |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Time Factors Respiratory rate Aconitine Tetrodotoxin Voltage-Gated Sodium Channels Pharmacology Electrocardiography Mice chemistry.chemical_compound Respiratory Rate Heart Rate medicine Animals Respiratory system Mice Inbred ICR Cardiotoxicity Myocardium musculoskeletal neural and ocular physiology Sodium channel Arrhythmias Cardiac General Medicine medicine.disease Oxygen Disease Models Animal chemistry Toxicity Ventricular fibrillation Anti-Arrhythmia Agents Biomarkers Sodium Channel Blockers |
| Zdroj: | Journal of Nippon Medical School. 80:350-361 |
| ISSN: | 1347-3409 1345-4676 |
| DOI: | 10.1272/jnms.80.350 |
| Popis: | Aconitine, well-known for its high cardiotoxicity, causes severe arrhythmias, such as ventricular tachycardia and ventricular fibrillation, by opening membrane sodium channels. Tetrodotoxin, a membrane sodium-channel blocker, is thought to antagonize aconitine activity. Tetrodotoxin is a potent blocker of the skeletal muscle sodium-channel isoform Na(v)1.4 (IC50 10 nM), but micromolar concentrations of tetrodotoxin are required to inhibit the primary cardiac isoform Na(v)1.5. This suggests that substantial concentrations of tetrodotoxin are required to alleviate the cardiac toxicity caused by aconitine. To elucidate the interaction between aconitine and tetrodotoxin in the cardiovascular and respiratory systems, mixtures of aconitine and tetrodotoxin were simultaneously administered to mice, and the effects on electrocardiograms, breathing rates, and arterial oxygen saturation were examined. Compared with mice treated with aconitine alone, some mice treated with aconitine-tetrodotoxin mixtures showed lower mortality rates and delayed appearance of arrhythmia. The decreased breathing rates and arterial oxygen saturation observed in mice receiving aconitine alone were alleviated in mice that survived after receiving the aconitine-tetrodotoxin mixture; this result suggests that tetrodotoxin is antagonistic to aconitine. When the tetrodotoxin dose is greater than the dose that can block tetrodotoxin-sensitive sodium channels, which are excessively activated by aconitine, tetrodotoxin toxicity becomes prominent, and the mortality rate increases because of the respiratory effects of tetrodotoxin. In terms of cardiotoxicity, mice receiving the aconitine-tetrodotoxin mixture showed minor and shorter periods of change on electrocardiography. This finding can be explained by the recent discovery of tetrodotoxin-sensitive sodium-channel cardiac isoforms (Na(v)1.1, 1.2, 1.3, 1.4 and 1.6). |
| Databáze: | OpenAIRE |
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