The role of iron in the NADPH-dependent lipid peroxidation due to glutathione depletion by phorone.

Enhanced NADPH-dependent LPO in rat liver postmitochondrial supernatants in vitro due to depletion of GSH by treatment with phorone (diisopropylidene acetone) in vivo was inhibited by Fe2+-chelating agents (desferrioxamine, DETAPAC), but not by scavengers of .O2-, H2O2, singlet oxygen or .OH-radicals, indicating that a perferryl ion (Fe2+ . O2) is needed as an initiating factor. In vivo, rats treated with phorone (250 mg/kg i.p.) exhaled 1.4 times as much ethane within 4 h as compared to controls. Pretreatment with FeSO4 resulted in a 6.9-fold enhancement of LPO as compared to Fe2+-pretreated controls. Our results indicate that GSH-depletion results in a strong enhancement of NADPH-dependent LPO also in vivo, provided that an initiating factor is present.