Scheulen M E, Kappus H, Nienhaus A, Schmidt C G
J Cancer Res Clin Oncol. 1982;103(1):39-48. doi: 10.1007/BF00410304.
Covalent binding of 3H-labeled adriamycin metabolites to bovine serum albumin and microsomal protein is demonstrated in an aerobic incubation system with rat liver and rat heart microsomes, respectively, using exhaustive organic solvent extraction and gel chromatography. Covalent protein binding was dependent on active microsomes, NADPH, and oxygen and was inhibited by reduced glutathione and other sulfhydryl compounds. The anthracycline moiety was spectrophotometrically evidenced in the adriamycin metabolite(s) covalently bound to protein. Thus, enzymatic activation of adriamycin in the heart with consecutive covalent protein binding of reactive adriamycin semiquinone radicals may contribute to adriamycin cardiotoxicity.
在分别使用大鼠肝脏微粒体和大鼠心脏微粒体的需氧孵育系统中，通过彻底的有机溶剂萃取和凝胶色谱法，证明了3H标记的阿霉素代谢物与牛血清白蛋白和微粒体蛋白的共价结合。共价蛋白结合依赖于活性微粒体、NADPH和氧气，并受到还原型谷胱甘肽和其他巯基化合物的抑制。在与蛋白质共价结合的阿霉素代谢物中，通过分光光度法证实了蒽环类部分的存在。因此，心脏中阿霉素的酶促活化以及活性阿霉素半醌自由基的连续共价蛋白结合可能导致阿霉素心脏毒性。
