Herman E H, Zhang J, Chadwick D P, Ferrans V J
Center for Drug Evaluation and Research, Food and Drug Administration, Laurel, MD 20708, USA.
Cancer Chemother Pharmacol. 2000;45(4):329-34. doi: 10.1007/s002800050048.
To compare the protective effects of amifostine and dexrazoxane against the chronic toxicity induced by doxorubicin in spontaneously hypertensive rats (SHR).
The animals were pretreated with amifostine (200 mg/kg. i.p.), dexrazoxane (25 mg/kg, i.p.) or saline 30 min before the administration of doxorubicin (1 mg/kg, i.v.), once-weekly for 12 weeks. Control animals received similar amounts of amifostine or saline. The SHR underwent necropsy examination 1 week after the last dosing, and cardiac, renal, and gastrointestinal lesions were graded semiquantitatively.
Amifostine and dexrazoxane provided equal degrees of protection against the renal toxicity of doxorubicin. However, dexrazoxane was more cardioprotective than amifostine, and prevented the mortality induced by doxorubicin. This mortality was not decreased by pretreatment with amifostine. The loss of body weight caused by doxorubicin was actually worsened by coadministration of amifostine.
Compared to dexrazoxane, amifostine provided a comparable degree of protection against the nephrotoxicity of doxorubicin, but was less cardioprotective and did not prevent the mortality and loss of body weight produced by doxorubicin. These differences may be related to the fact that amifostine may act as a scavenger of reactive oxygen species, whereas dexrazoxane may prevent their formation.
比较氨磷汀和右丙亚胺对阿霉素诱导的自发性高血压大鼠（SHR）慢性毒性的保护作用。
在给予阿霉素（1mg/kg，静脉注射）前30分钟，动物分别接受氨磷汀（200mg/kg，腹腔注射）、右丙亚胺（25mg/kg，腹腔注射）或生理盐水预处理，每周一次，共12周。对照动物接受等量的氨磷汀或生理盐水。在最后一次给药后1周，对SHR进行尸检，对心脏、肾脏和胃肠道病变进行半定量分级。
氨磷汀和右丙亚胺对阿霉素的肾毒性提供了同等程度的保护。然而，右丙亚胺比氨磷汀对心脏的保护作用更强，并预防了阿霉素诱导的死亡。氨磷汀预处理并未降低这种死亡率。氨磷汀与阿霉素共同给药实际上使阿霉素引起的体重减轻恶化。
与右丙亚胺相比，氨磷汀对阿霉素的肾毒性提供了相当程度的保护，但对心脏的保护作用较弱，且不能预防阿霉素引起的死亡和体重减轻。这些差异可能与以下事实有关：氨磷汀可能作为活性氧的清除剂，而右丙亚胺可能预防其形成。
