Effects of 1,4-naphthoquinone derivatives on red blood cell metabolism.

The effect on red blood cell metabolism of a series of substituted 1,4-naphthoquinones has been investigated. 2-Methoxy-1,4-naphthoquinone was found to be a potent oxidative compound, generating hydrogen peroxide in erythrocytes and causing both methemoglobin formation and glutathione depletion in the absence of glucose. Flux of glucose through both glycolysis and the hexose monophosphate shunt was stimulated. 2-Hydroxy- and 2,3-dihydroxy-1,4-naphthoquinone were less oxidative. Both compounds caused oxidation of glutathione and formation of hydrogen peroxide with corresponding stimulation of the hexose monophosphate shunt, but did not cause methemoglobin formation. 2-Hydroxy-3-alkyl-1,4-naphthoquinones were not oxidative but did increase the flux of glucose through glycolysis, possibly reflecting membranal damage. The in vitro oxidative effects of these substances do not correlate with their hemolytic activity in rats, indicating that factors other than oxidative damage are important in mediating the in vivo toxicity of these substances.