N-ACETYLCYSTEINE PROTECTS FROM GLUTATHIONE DEPLETION IN RATS EXPOSED TO HYPEROXIA

Background: N-acetylcysteine (NAC) may protect against oxidative injur y by providing cysteine for glutathione (GSH) biosynthesis or by direc t reactions with electrophiles. The have recently shown that hyperoxic exposure of rats prior to liver perfusion is associated with signific ant decreases in hepatic GSH and significant changes in biliary amino acid concentrations. We hypothesized that NAC administration during hy peroxic exposure would prevent depletion of hepatic GSH by providing c ysteine for GSH biosynthesis. Methods: NAC was administered during two conditions known to induce GSH depletion: hyperoxic exposure and bioc hemical inhibition of GSH synthesis using buthionine sulfoximine (BSO) . After 48 tours, GSH concentrations in bile, liver and perfusate and biliary amino acid concentrations were determined using isolated perfu sed liver preparations. Results: Administration of NAC to rats maintai ned in normoxic or hyperoxic conditions: prior to liver perfusion, res ulted in dose-dependent increases in GSH concentrations in bile, liver and perfusate, increases in bile now rates and changes in biliary ami no acid concentrations. When BSO was given concurrently with NAC in no rmal or hyperoxic conditions, these effects were not observed, and oxi dant stress was evident. Conclusions: NAC prevents oxidant stress duri ng hyperoxic exposure, most likely by supplying cysteine as a precurso r for GSH synthesis.