CYCLOPHOSPHAMIDE CYSTITIS - IDENTIFICATION OF ACROLEIN AS THE CAUSATIVE AGENT
CYCLOPHOSPHAMIDE CYSTITIS - IDENTIFICATION OF ACROLEIN AS THE CAUSATIVE AGENT
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DOI：
10.1016/0006-2952(79)90222-3
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发表时间：
1979-01-01
影响因子：
5.8
通讯作者：
COX, PJ
中科院分区：
文献类型：
--
作者：
COX, PJ
本文研究了抗肿瘤药物环磷酰胺{2[bis(2-chloroethyl)amino]tetrahydro-2H-1，3，2-oxazaphosphorine_2-氧化物和异环磷酰胺[3-(2-chloroethyl)-2-(2-chloroethylamino)tetrahydro-1，3，2-oxazaphosphorine_2-氧化物对大鼠出血性膀胱炎的影响。在该模型中找到了N-乙酰-L-半胱氨酸的最佳毒性保护条件。环磷酰胺的最终烷基化代谢物磷酰胺芥末和5，5-二甲基环磷酰胺对膀胱的影响很小，后者可以代谢，但不形成细胞毒性产物。然而，二乙基环磷酰胺[[2-(diethylamino)tetrahydro-2H-1，3，2-oxazaphosphorine 2-氧化物]对雄性大鼠造成严重的膀胱炎，对雌性大鼠有显著的损害，但损害范围较小；N-乙酰半胱氨酸对这种毒性有保护作用。由于丙烯醛是二乙基环磷酰胺唯一具有活性和细胞毒性的代谢物，因此证明了丙烯醛在环磷酰胺膀胱炎中的作用。
Hemorrhagic cystitis of the bladder caused by the antitumour agents cyclophosphamide {2[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide} and ifosfamide [3-(2-chloroethyl)-2-(2-chloroethylamino)tetrahydro-1,3,2-oxazaphosphorine 2-oxide] was studied in the rat. Optimum conditions in this model for protection from toxicity by N-acetyl-L-cysteine were found. Phosphoramide mustard, the ultimate alkylating metabolite of cyclophosphamide, and 5,5-dimethylcyclophosphamide, which is metabolized but forms no cytotoxic products, had minimal effects on the bladder. However, diethylcyclophosphamide [2-(diethylamino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide] caused severe cystitis in the male rat, and significant, but less extensive damage, in the female rat; N-acetyl-L-cysteine protection against this toxicity was demonstrated. As acrolein is the only reactive and cytotoxic metabolite of diethylcyclophosphamide, the role of acrolein as the causative agent in cyclophosphamide cystitis was proven.