Bronson R T, Henderson I C, Fixler H
Cancer Treat Rep. 1982 Jun;66(6):1349-55.
The effects of long-term administration of doxorubicin in adult rabbits and in a rhesus monkey were studied. Eleven rabbits were given cumulative doses of 2--24 mg/kg over a period of 5--28 weeks. The monkey received a total of 20 mg/kg during a 10-month period. One rabbit exhibited hind leg paresis, but all of the other animals in the study remained clinically free of neurologic signs. Rabbits given less than 12 mg/kg of doxorubicin had only mild degenerative changes in dorsal roots and a few necrotic neurons in the dorsal root ganglia, but these lesions were much more severe in all rabbits when a cumulative dose greater than 16 mg/kg was given. The monkey also had severe ganglioneuropathy, suggesting that primates may also be susceptible to this toxic effect of doxorubicin. Although neurotoxicity has not been observed with the dose schedules of doxorubicin used in clinical practice, the tendency of this drug to damage both postmitotic neural and cardiac cells may provide added understanding of the clinically important doxorubicin cardiomyopathy.
研究了阿霉素长期给药对成年兔和恒河猴的影响。11只兔在5 - 28周内给予累积剂量为2 - 24mg/kg的阿霉素。这只猴子在10个月内共接受了20mg/kg的阿霉素。一只兔出现后腿轻瘫，但研究中的所有其他动物临床上均未出现神经体征。给予低于12mg/kg阿霉素的兔仅在背根有轻度退行性改变，背根神经节有少数坏死神经元，但当累积剂量大于16mg/kg时，所有兔的这些病变都严重得多。这只猴子也有严重的神经节神经病，表明灵长类动物可能也易受阿霉素这种毒性作用的影响。虽然在临床实践中使用的阿霉素剂量方案未观察到神经毒性，但这种药物损害有丝分裂后神经细胞和心肌细胞的倾向可能有助于进一步理解临床上重要的阿霉素心肌病。
