Anti-cancer quinones cause oxidative stress and endothelial dysfunction

We examined the effects of the anti-tumor quinones, menadione (MQ) and doxorubicin (DOX), on endothelial cell (EC) barrier dysfunction in bovine pulmonary artery EC (BPAEC) monolayers. MQ (15 muM, 4-h incubation) and DOX (0.86 muM, 24-h incubation) caused 7-8-fold increases in albumin permeability with coincident decreases in EC glutathione levels. Both agents caused significant reduction in the activity of glucose-6-phosphate dehydrogenase (G6PDH), the enzyme that produces the nicotinamide adenine dinucleotide phosphate (NADPH) used to maintain intracellular reduced glutathione (GSH) levels during an oxidative stress. These results suggest that quinone-induced oxidative stress coupled with G6PDH inhibition predispose ECs to barrier dysfunction.