The effect of glutathione modulation on the concentration of homocysteine in plasma of rats

Elevated plasma homocysteine concentration in humans is associated with inc reased risk of arteriosclerosis and ischaemic heart disease. We studied whe ther the plasma homocysteine concentration could be changed by administrati on of drugs that modulate the concentration of glutathione in both plasma a nd tissue. Male wistar rats received reduced glutathione (0.5 mmol/kg), N-a cetylcysteine (0.5 mmol/kg), L-buthionine-[S,R]-sulfoximine (2 mmol/kg) or Ringer acetate intravenously. Twenty min, later an arterial blood sample wa s drawn for the measurement of homocysteine and other thiols in the plasma. The thiols were quantified by reversed-phase ion-pair liquid chromatograph y and fluorescence detection. The total homocysteine concentration in plasm a of fasted rats was 6.1+/-0.5 mu M. Intravenous administration of reduced glutathione or N-acetylcysteine reduced the homocysteine concentration in p lasma significantly by 51% to 3.0+/-0.3 mu M and 63% to 2.2+/-0.2 mu M, res pectively (P<0.05). In contrast, L-buthionine-[S,R]-sulfoximine increased t he concentration of homocysteine by 41% to 8.6+/-0.6 mu M (P<0.05). The glu tathione concentration in plasma was 19.5+/-1.9 mu M in controls and was un changed by N-acetylcysteine administration. Reduced glutathione increased p lasma glutathione to 379.7+/-22.9 mu M (P<0.05), whereas L-buthionine-[S, R ]-sulfoximine lowered the plasma glutathione concentration to 5.3+/-0.4 mu M. Homocysteine was negatively correlated to the glutathione (r=-0.399, P<0 .01) and the cysteine (r=-0.52, P<0.01) concentrations in plasma. Our concl usion is that modulation of the glutathione levels influences the concentra tion of homocysteine in plasma of rats.