Menadione-induced cytotoxicity in rat platelets: Absence of the detoxifying enzyme, quinone reductase

Abstract

The elevation of intracellular Ca2+ in various tissue through oxidative stress induced by menadione has been well documented. Increase of Ca2+ level in platelets results in aggregation of platelets. To test the hypothesis that menadione-induced Ca2+ elevations can play a role in platelet aggregation, we have studied the effect of menadione on aggregation of platelets isolated from female rats. Treatment with menadione to platelet rich plasma (PRP), which proved to be an adequate system, appeared to induce dose-dependent turbidity changes of platelets up to 60%, as determined by aggregometry. However, exposure of PRP to menadione leads to a loss of cell viability, as measured by lactate dehydrogenase (LDH) leakage, suggesting that menadione might induce cell lysis rather than aggregation of platelets. Turbidity changes induced by menadione were unaffected by addition of dicoumarol, which is a quinone reductase (QR) inhibitor. Consistent with these findings, no activity of QR was detected in any subcellular fractions of platelets. These data, which indicate an absence of the QR detoxifying pathway, suggest that platelets may be more susceptible to menadione-induced cytotoxicity than certain other cell, such as hepatocytes.