Zeng Z X, Bao D Y, Xiao Y, Liao N G, Miao S K, Liu Y Q, Li G R, Liao J
Hua Xi Yi Ke Da Xue Xue Bao. 1989 Sep;20(3):303-6.
Acute toxicity of mitoxantrone (DHAQ) synthetized by Department of Organic Chemistry, School of Pharmacy, WCUMS was studied in mice and dogs. The toxic effects were compared with those of adriamycin (ADR). The LD50 were 6.6 +/- 1.3 and 7.1 +/- 1.6 mg/kg DHAQ, 7.9 +/- 2.1 and 10.7 +/- 2.2 mg/kg ADR (P = 0.95) respectively on observation with a single dose i.v. and i.p., for 21 days in Kunming mice. The toxicity appeared to be delayed with DHAQ and ADR. The earliest death occurred on 4th day after treatment in mice. In the third week still a few died. There were obvious decreases in WBC counts in the peripheral blood of mice receiving either 1-2.5 mg/kg DHAQ or 2.5-5 mg/kg ADR with a single dose i.p.. The WBC count could return to normality after 3 weeks with the withdrawal of the drugs. On electron microscopic examination of myocardial samples from mice 4 days after a single dose of 20 mg/kg DHAQ i.p., mitochondria swelling and vacuoles formation in some cells were shown. Besides the above-mentioned changes, some myocytes exhibited disorientation and loss of myofilaments in the mice which received equivalent dose of ADR. In dogs anaesthetized a temporary falling of blood pressure and slowing of heart rate were observed following 5-10 mg/kg DHAQ i.p.. When a dose of 50-100 mg/kg was given, the blood pressure dropped continuously until death.
对温州医科大学药学院有机化学教研室合成的米托蒽醌（DHAQ）进行了小鼠和犬的急性毒性研究。将其毒性作用与阿霉素（ADR）的毒性作用进行了比较。昆明小鼠单次静脉注射和腹腔注射给药21天的观察结果显示，DHAQ的半数致死量分别为6.6±1.3和7.1±1.6mg/kg，ADR的半数致死量分别为7.9±2.1和10.7±2.2mg/kg（P = 0.95）。DHAQ和ADR的毒性似乎有延迟。最早在治疗后第4天出现死亡。在第三周仍有少数死亡。单次腹腔注射1-2.5mg/kg DHAQ或2.5-5mg/kg ADR的小鼠外周血白细胞计数明显下降。停药3周后白细胞计数可恢复正常。单次腹腔注射20mg/kg DHAQ 4天后对小鼠心肌样本进行电子显微镜检查，结果显示部分细胞线粒体肿胀和空泡形成。除上述变化外，接受等量ADR的小鼠部分心肌细胞出现排列紊乱和肌丝丢失。对麻醉犬腹腔注射5-10mg/kg DHAQ后观察到血压暂时下降和心率减慢。当给予50-100mg/kg剂量时，血压持续下降直至死亡。
