Gralla E J, Coleman G L, Osbaldiston G W, Kashgarian M, Jonas A M
Cancer Chemother Rep. 1975 Nov-Dec;59(6):1071-81.
The toxic effects of cytembena in beagle dogs and rhesus monkeys were investigated with the drug given as single or daily iv injections in doses ranging from 12.5 to 200 mg/kg/day to dogs and 6.25 to 50 mg/kg/day to monkeys. Renal tubular damage was a major drug- and dose-related finding in both species and was clinically indicated by an accompanying uremia, elevated serum creatinine, and proteinuria. In the kidney, the primary lesion was cellular necrosis and desquamation of the distal tubular epithelium in animals given the lowest toxic doses. More severe but similar histologic changes produced by this drug were further characterized by single dose studies in mice which showed renal mitochondrial swelling and disruption plus generalized cell swelling as progressive, subcellular developments which were well established 24 hours after treatment. Cellular regeneration in the renal tubular epithelium was found in dogs and monkeys retained 6 weeks for observation after treatment, although functional recovery was inconsistent. A toxic effect to lymphoid tissue was an additional finding which is described.
对比格犬和恒河猴进行了塞替派的毒性研究，该药物通过静脉注射，每日一次或单次给药，犬的剂量范围为12.5至200mg/kg/天，猴的剂量范围为6.25至50mg/kg/天。肾小管损伤是这两个物种中与药物和剂量相关的主要发现，临床症状为伴有尿毒症、血清肌酐升高和蛋白尿。在肾脏中，给予最低毒性剂量的动物，主要病变是远端肾小管上皮细胞坏死和脱落。该药物产生的更严重但相似的组织学变化，通过对小鼠的单次给药研究进一步表征，结果显示肾线粒体肿胀和破坏，以及全身细胞肿胀，这些是在治疗后24小时内逐渐形成的亚细胞变化。在治疗后保留观察6周的犬和猴中发现肾小管上皮细胞再生，尽管功能恢复并不一致。另外还发现该药物对淋巴组织有毒性作用。
