巯基化合物对尿毒性氮杂磷类化合物的解毒作用。
Detoxification of urotoxic oxazaphosphorines by sulfhydryl compounds.
作者信息
Brock N, Pohl J, Stekar J
出版信息
J Cancer Res Clin Oncol. 1981;100(3):311-20. doi: 10.1007/BF00410691.
Abstract
Urotoxic side effects, especially hemorrhagic cystitis, have so far been a limiting factor in the therapeutic use of cyclophosphamide (Endoxan), ifosfamide (Holoxan), and trofosfamide (Ixoten). The uroprotective agent mesna (Uromitexan) allows regional detoxification in the kidney and the urinary tract, and thus clinical prevention of the urotoxic side effects of the above cytostatics. The uroprotective mechanism of mesna is based on the formation of nontoxic additive compounds with acrolein and 4-hydroxy-metabolites. In the body, mesna is rapidly transformed into its biologically inert disulfide. After glomerular filtration mesna disulfide is rapidly reduced by reacting with the glutathion system and elimination in the urine as a free thiol compound, further detoxifying the aggressive oxazaphosphorine metabolites.
摘要
尿毒性副作用，尤其是出血性膀胱炎，迄今为止一直是环磷酰胺（癌得星）、异环磷酰胺（和乐生）和曲磷胺（艾托替星）治疗应用中的一个限制因素。尿路保护剂美司钠（巯乙磺酸钠）可在肾脏和尿路中进行局部解毒，从而在临床上预防上述细胞抑制剂的尿毒性副作用。美司钠的尿路保护机制基于与丙烯醛和4 - 羟基代谢产物形成无毒加成化合物。在体内，美司钠迅速转化为其生物惰性的二硫化物。肾小球滤过后，美司钠二硫化物通过与谷胱甘肽系统反应迅速还原，并以游离硫醇化合物形式经尿液排出，进一步使具有侵袭性的氧氮磷啶代谢产物解毒。
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