Drug interaction effects on antitumour drugs (XV): Disulfiram as protective agent against cyclophosphamide-induced urotoxicity without compromising antitumour activity in mice.

Drug interaction effects on antitumour drugs (XV): Disulfiram as protective agent against cyclophosphamide-induced urotoxicity without compromising antitumour activity in mice.
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抗肿瘤药物的药物相互作用影响 (XV):双硫仑作为保护剂,对抗环磷酰胺诱导的尿毒性,且不影响小鼠的抗肿瘤活性。

DOI:
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发表时间:
1994
期刊:
Acta Pharmacologica et Toxicologica
影响因子:
--
通讯作者:
K. Sasaki
K. Sasaki
中科院分区:
--
文献类型:
--
作者:
M. Ishikawa;T. Aoki;S. Yomogida;Y. Takayanagi;K. Sasaki

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The prevention of cyclophosphamide-induced urotoxicity by disulfiram was studied in mice. A single dose of cyclophosphamide (100-400 mg/kg, intraperitoneally) produced a significant dose-dependent increase in urinary bladder weight within 48 hr of treatment. Disulfiram prevented cyclophosphamide-induced bladder damage in a dose-dependent manner in mice when orally administered simultaneously with antitumour agents, but failed to diminish the acute toxicity, leukocytotoxicity and immunotoxicity of cyclophosphamide. The protective effect of disulfiram on the bladder was critically dependent on administration timing. Oral administration of disulfiram between 60 min. before and 60 min. after the injection of cyclophosphamide was found to be effective. The optimum time was simultaneous administration of both drugs. Diethyldithiocarbamate and carbon disulfide, metabolites of disulfiram, prevented cyclophosphamide-induced bladder damage when administered simultaneously with cyclophosphamide 1 to, 3 or 5 hr afterwards. Disulfiram slightly potentiated the antitumour activity of cyclophosphamide against Sarcoma 180 or EL-4 leukaemia in vivo when administered simultaneously with cyclophosphamide. In contrast, diethyldithiocarbamate or carbon disulfide did not interfere with cyclophosphamide antitumour activity when administered 3 hr after cyclophosphamide. From these preliminary studies, disulfiram appears to be a likely candidate for protection against cyclophosphamide-induced urotoxicity without compromising the therapeutic utility of the alkylating agent.
DOI: --
发表时间: 1981
期刊: Cancer treatment reports
影响因子: --
作者:
M. Colvin;J. Hilton
通讯作者: M. Colvin;J. Hilton