title: Metabolism and cytotoxicity of menadione and its metabolite in rat platelets.
abstract: 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.
authors.affiliation: College of Pharmacy, Seoul National University, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Chung
authors.forename: D C
authors.initials: DC
authors.lastname: Seo
authors.forename: S H
authors.initials: SH
authors.lastname: Chung
authors.forename: J Y
authors.initials: JY
authors.lastname: Lee
authors.forename: S A
authors.initials: SA
authors.lastname: Seung
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006490:Hemostatics / Q000378:metabolism / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010949:Plasma / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014812:Vitamin K / Q000378:metabolism / Q000633:toxicity*
chemical_list: D006490:Hemostatics; D014812:Vitamin K; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D010100:Oxygen