評估以圓水蚤作安眠藥Zolpidem及Benzodiazepine之生物毒性檢測之可行性

目的：此實驗是研究安眠藥對於水生圓水蚤的心跳效應，目的是希望建立以圓水蚤為模式用以測試毒物對人類疾病之影響。方法：本研究使用來自實驗室自行培養的第五代水蚤為對象，以硬水和實驗室自製的培養基進行培養。選用兩種具代表性的安眠藥Zolpidem和Benzodiazepine，配製成一系列的濃度。之後進行半數致死濃度(LC50)、半數效應濃度(EC50)和心跳速率的量測，判斷安眠藥對圓水蚤的毒性效應。結果：新生圓水蚤靜置暴露在Zolpidem tartrate(Stilnox)48小時其LCS50值為72.783 mg/L，靜置暴露在Benzodiazepine(BZD)48小時其LC50值為67.906 mg/L。圓水蚤胚胎暴露在Stilnox和BZD 48小時其EC50值分別為4.572和0.739 mg/L。兩種藥物引起的急毒性都隨暴露時間增長而增加。在心跳速率的量測，和控制組相較，Stilnox會使跳速率減少3-25%，BZD則是減少6-41%。結論：本實驗證實Stilnox和BZD會引起圓水蚤劇烈的心跳速率降低和心律不整。將來，適合發展以圓水蚤為模型，作為生物或醫學上藥物毒性之檢測。
Purpose: The aim of the experiments described here was to show whether Daphnia pulex could be used to investigate the effects of sleeping pill on the heart and to establish D. pulex as a model for investigating the side effect in human disease. Methods: The research used the 5(superscript th) generation water flea cultivated by the laboratory itself as the experiment material, adopted the nature-imitating water (hard water), and selected two representative sleeping pills to prepare for a density series, to carry out a series of experiments, including: acute toxicity test for LC50, EC50 values and measurement of the heart beat rate, after Zolpidem and Benzodiazepine treated. Results: D. pulex neonate 48h-LC50 values of two pharmaceuticals tested in the present study were 72.783 mg/L for Zolpidem tartrate (Stilnox) and 67.906 mg/L for Benzodiazepine (BZD). D. pulex embryo 48h-EC50 values of two pharmaceuticals tested in the present study were 4.572 mg/L for Stilnox and 0.739 mg/L for BZD. The acute toxicity to D. pulex increased with the duration of exposure for both the sleeping pills, which present a dose response reaction. The sleeping pills effects on the Daphnia heart beat rate are significantly different with the control group. Stilnox could decreased 3-25% of heart beat rate than the control group, and BZD decreased 6-41% of heart beat rate than the control group. The effect on Daphnia heart beat rate of BZD was unexpectedly higher than Stilnox. Conclusion: Here, we report that sleeping pill, at concentrations found in Zolpidem and Benzodiazepine, caused a dramatic decrease in D. pulex heart beat rate and induced severe arrhythmia. Our results provide further evidence of D. pulex as a unique model system in biology and medicine.