The metabolism of menadione (2-methyl-1,4-naphthoquinone) by isolated hepatocytes. A study of the implications of oxidative stress in intact cells.
The cytotoxic effects of many quinones are thought to be mediated through their one-electron reduction to semiquinone radicals, which subsequently enter redox cycles with molecular oxygen to produce active oxygen species and oxidative stress. The two-electron reduction of quinones to diols, mediated by DT-diaphorase (NAD(P)H: (quinone-acceptor) oxidoreductase), may therefore represent a detoxifying pathway which protects the cell from the formation of these reactive intermediates. By using menadione (2-methyl-1,4-naphthoquinone) and isolated hepatocytes, the relative contribution of the two pathways to quinone metabolism has been studied and a protective role for DT-diaphorase demonstrated. Moreover, in the presence of cytotoxic concentrations of menadione rapid changes in intracellular thiol and Ca2+ homeostasis were observed. These were associated with alterations in the surface structure of the hepatocytes which may be an early indication of cytotoxicity.
D000818:Animals; D001728:Dicumarol / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism; D013499:Surface Properties; D014812:Vitamin K / Q000378:metabolism*
D014812:Vitamin K; D001728:Dicumarol; D013482:Superoxide Dismutase; D005978:Glutathione