Metabolism and cytotoxicity of menadione and its metabolite in rat platelets
Metabolism and cytotoxicity of menadione and its metabolite in rat platelets
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DOI：
10.1006/taap.1996.8048
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发表时间：
1997-02-01
影响因子：
3.8
通讯作者：
Seung, SA
中科院分区：
文献类型：
--
作者：
Chung, JH;Seo, DC;Seung, SA
Previous studies suggest that menadione is cytotoxic to rat platelets by oxidative stress. In order to elucidate the mechanism of this toxicity, metabolism of menadione and the cytotoxicity of a metabolite, menadione-glutathione conjugate (MEN-SG), were investigated in platelet rich plasma and washed platelet (WP) systems. When menadione was incubated in platelets, the primary metabolite was MEN-SG, which was excreted into the incubation medium. Incubation of subcellular fractions of platelets with synthetic MEN-SG led to increases in oxygen consumption that were similar to the parent compound, menadione. However, unlike menadione, exposure of MEN-SG to intact platelets in WP system neither resulted in increased oxygen consumption nor induced cell lysis as measured by lactate dehydrogenase leakage. In contrast to menadione, levels of MEN-SG in the incubation medium were unaffected by the presence of platelets, suggesting that MEN-SG was not consumed (or taken up) by platelets. These results indicate that even though MEN-SG was able to induce oxidative stress within platelets as potently as menadione itself, the MEN-SG formation from menadione in platelets appeared not to contribute to menadione's cytotoxicity. This lack of MEN-SG toxicity was likely due to its rapid excretion outside the cells. (C) 1997 Academic Press.
