Phospholipid hydroperoxides are detoxified by phospholipase A2 and GSH peroxidase in rat gastric mucosa.

The aim of this study was to determine the metabolic fate of phospholipid hydroperoxides (PLOOH) in rat gastric mucosa. Here we report evidence concerning the mechanism for PLOOH detoxification in gastric mucosa homogenate. Analysis by the TLC blot technique showed that the gastric mucosa has the highest potential to eliminate 1-palmitoyl-2-linoleoyl-phosphatidylcholine hydroperoxides (PL-PtdChoOOH) compared with the intestinal mucosa and liver. Major products detected after incubation with gastric mucosa were the partially reduced linoleic acid hydroperoxides (LAOOH) and lysophosphatidylcholine, indicating the involvement of phospholipase A2 (PLA2) in the elimination pathway. Using unilamellar vesicles, we demonstrated that gastric mucosal PLA2 does not distinguish between PLOOH and intact phospholipids. Although gastric mucosal PLA2 activity efficiently eliminated excess amounts of PLOOH, the complete reduction of LAOOH was dependent on the supply of exogenous GSH. In a separate experiment, administration of egg yolk PtdChoOOH to rats for 6 d significantly elevated GSH peroxidase (GPx) activity in the gastric mucosa. We concluded that excess amounts of PLOOH are efficiently eliminated through the hydrolysis by PLA2, and the subsequent reduction of FA hydroperoxide by GPx is the critical step for complete detoxification of oxidized phospholipids in the stomach.