N-acetylcysteine protects from glutathione depletion in rats exposed to hyperoxia

ABSTRACT. Background: N-acetylcysteine (NAC) may protect against oxidative injury by providing cysteine for glutathione (GSH) biosynthesis or by direct reactions with electrophiles. We have recently shown that hyperoxic exposure of rats prior to liver perfusion is associated with significant decreases in he-patic GSH and significant changes in biliary amino acid concen-trations. We hypothesized that NAC administration during hyperoxic exposure would prevent depletion of hepatic GSH by providing cysteine for GSH biosynthesis. Methods: NAC was ad-ministered during two conditions known to induce GSH deple-tion: hyperoxic exposure and biochemical inhibition of GSH syn-thesis using buthionine sulfoximine (BSO). After 48 hours, GSH concentrations in bile, liver and perfusate and biliary amino acid concentrations were determined using isolated perfused liver preparations. Results: Administration of NAC to rats maintaine