Glutathione and N-acetylcysteine reduce gastric mucosal blood flow in rats

Glutathione has been studied as a possible mediator in gastric mucosal protection and healing, but its extracellular function is not fully understood. This study evaluates blood flow changes in normal gastric mucosa secondary to glutathione modulation under stable central hemodynamic conditions. Thiol substances were quantified by reverse-phase ion-pair liquid chromatography and fluorescence detection. Central hemodynamics remained stable when glutathione and N-acetylcysteine were administered in a dose of 0.5 mmol/kg. Higher doses than 0.5 mmol/kg of glutathione and N-acetylcysteine caused unstable hemodynamics. Glutathione (0.5 mmol/kg intravenously) and N-acetylcysteine (0.5 mmol/kg intravenously) reduced corpus mucosal blood flow by 28% and 26% (P < 0.0005), respectively, and glutathione reduced antral mucosa blood flow by 22% (P < 0.01). L-Buthionine-[S,R]-sulfoximine (2 mmol/kg intravenously) did not effect gastric mucosal blood flow. Cysteine content in mucosa and plasma increased while mucosal glutathione levels were largely unchanged after administration of reduced glutathione and N-acetylcysteine. Plasma glutathione only increased after injection of glutathione. L-Buthionine-[S,R]-sulfoximine reduced the glutathione level in both plasma and mucosa. We conclude that glutathione and N-acetylcysteine reduce gastric mucosal blood flow and that the effect may be related to increased cysteine levels in plasma or mucosa.