PROTECTION BY N-ACETYLCYSTEINE OF CYCLOPHOSPHAMIDE METABOLISM-RELATED INVIVO DEPRESSION OF MIXED-FUNCTION OXYGENASE ACTIVITY AND INVITRO DENATURATION OF CYTOCHROME-P-450
PROTECTION BY N-ACETYLCYSTEINE OF CYCLOPHOSPHAMIDE METABOLISM-RELATED INVIVO DEPRESSION OF MIXED-FUNCTION OXYGENASE ACTIVITY AND INVITRO DENATURATION OF CYTOCHROME-P-450
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DOI：
10.1016/0006-291x(80)91147-x
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发表时间：
1980-01-01
影响因子：
3.1
通讯作者：
MARINELLO, AJ
中科院分区：
文献类型：
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作者：
BERRIGAN, MJ;GURTOO, HL;MARINELLO, AJ
环磷酰胺（CP）[一种抗肿瘤药物]在高剂量或重复剂量下会导致肝脏混合功能加氧酶活性的抑制。这归因于CP的代谢产物丙烯醛与细胞色素P-450中的巯基之间的相互作用。证明了N-乙酰半胱氨酸对丙烯醛诱导的[大鼠]细胞色素P-450体外变性和CP相关的[大鼠]混合功能加氧酶体内抑制的保护作用。CP和提供游离巯基的无害化学品的共同施用应有助于通过降低一些毒性和/或通过允许使用较低但有效剂量的CP重复治疗来增强CP的治疗指数。
Cyclophosphamide (CP) [an antineoplastic drug] at high or repeated doses results in the depression of mixed function oxygenase activities of the liver. This is attributed to the interaction between acrolein, a metabolite of CP, and sulfhydryl groups in cytochrome P-450. The protection afforded by N-acetylcysteine against acrolein-induced denaturation of [rat] cytochrome P-450 in vitro and CP-related depression of [rat] mixed function oxygenase in vivo is demonstrated. Co-administration of CP and innocuous chemicals that provide free sulfhydryl groups should be useful in enhancing the therapeutic index of CP by reducing some of the toxicity and/or by allowing the use of repeated treatment with lower but effective doses of CP.