Suzuki T, Minamide S, Iwasaki T, Yamamoto H, Kanda H
Department of Laboratory Sciences, Gunma University School of Health Sciences, Japan.
Invest New Drugs. 1997;15(3):219-25. doi: 10.1023/a:1005862730941.
The degree of cardiotoxicity of SM-5887 compared with that of doxorubicin was investigated in rabbits. Two experimental groups were administered high and low doses of SM-5887, respectively. One group was administered doxorubicin and another group was administered the vehicle only were prepared as positive and negative controls, respectively. Drugs were intravenously administered 3 times a week for 8 weeks. At terminus, electrocardiograms were recorded under anesthesia. The blood was collected for haematology and blood biochemistry analyses. Myocardial tissue damage was evaluated using light and electron microscopy. In the electrocardiogram study, prolongation of QTc interval and ST-T change were observed in rabbits administered SM-5887 and doxorubicin. Morphological studies showed that myocardial tissue damage in animals administered SM-5887 was comparable to that in the negative controls, and less than that observed in the positive controls. The general toxicological investigations uniformly indicated lower toxicity in the SM-5887 group than in the doxorubicin group at equivalent dosages. In total, considering the results of antitumor efficacy studies comparing SM-5887 with doxorubicin, these results indicate that the cardiotoxicity of SM-5887 is very slight, and that the general toxicity of SM-5887 is lower than that of doxorubicin.
在兔子身上研究了SM - 5887与阿霉素相比的心脏毒性程度。分别给两个实验组给予高剂量和低剂量的SM - 5887。一组给予阿霉素，另一组仅给予赋形剂，分别作为阳性和阴性对照。药物每周静脉注射3次，共8周。实验结束时，在麻醉状态下记录心电图。采集血液进行血液学和血液生化分析。使用光学显微镜和电子显微镜评估心肌组织损伤。在心电图研究中，给予SM - 5887和阿霉素的兔子出现QTc间期延长和ST - T改变。形态学研究表明，给予SM - 5887的动物心肌组织损伤与阴性对照相当，且小于阳性对照。一般毒理学研究一致表明，在等效剂量下，SM - 5887组的毒性低于阿霉素组。总体而言，考虑到比较SM - 5887与阿霉素的抗肿瘤疗效研究结果，这些结果表明SM - 5887的心脏毒性非常轻微，且SM - 5887的一般毒性低于阿霉素。
