Ovrebø K K, Svardal A
Department of Surgery, University of Bergen, Haukeland University Hospital, Norway.
Pharmacol Toxicol. 2000 Sep;87(3):103-7. doi: 10.1111/j.0901-9928.2000.870301.x.
Elevated plasma homocysteine concentration in humans is associated with increased risk of arteriosclerosis and ischaemic heart disease. We studied whether the plasma homocysteine concentration could be changed by administration of drugs that modulate the concentration of glutathione in both plasma and tissue. Male wistar rats received reduced glutathione (0.5 mmol/kg). N-acetylcysteine (0.5 mmol/kg), L-buthionine-[S,R]-sulfoximine (2 mmol/kg) or Ringer acetate intravenously. Twenty min. later an arterial blood sample was drawn for the measurement of homocysteine and other thiols in the plasma. The thiols were quantified by reversed-phase ion-pair liquid chromatography and fluorescence detection. The total homocysteine concentration in plasma of fasted rats was 6.1+/-0.5 microM. Intravenous administration of reduced glutathione or N-acetylcysteine reduced the homocysteine concentration in plasma significantly by 51% to 3.0+/-0.3 microM and 63%, to 2.2 +/- 0.2 microM, respectively (P<0.05). In contrast, L-buthionine-[S,R]-sulfoximine increased the concentration of homocysteine by 41% to 8.6 +/- 0.6 microM (P<0.05). The glutathione concentration in plasma was 19.5 +/-1.9 microM in controls and was unchanged by N-acetylcysteine administration. Reduced glutathione increased plasma glutathione to 379.7 +/- 22.9 microM (P<0.05). whereas L-buthionine-[S R]-sulfoximine lowered the plasma glutathione concentration to 5.3 +/- 0.4 microM. 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 conclusion is that modulation of the glutathione levels influences the concentration of homocysteine in plasma of rats.
人体血浆同型半胱氨酸浓度升高与动脉硬化和缺血性心脏病风险增加相关。我们研究了给予能调节血浆和组织中谷胱甘肽浓度的药物是否可改变血浆同型半胱氨酸浓度。雄性Wistar大鼠静脉注射还原型谷胱甘肽（0.5 mmol/kg）、N-乙酰半胱氨酸（0.5 mmol/kg）、L-丁硫氨酸-[S,R]-亚砜亚胺（2 mmol/kg）或醋酸林格液。20分钟后采集动脉血样以测定血浆中的同型半胱氨酸和其他硫醇。通过反相离子对液相色谱和荧光检测对硫醇进行定量。禁食大鼠血浆中的总同型半胱氨酸浓度为6.1±0.5 μM。静脉注射还原型谷胱甘肽或N-乙酰半胱氨酸可使血浆中的同型半胱氨酸浓度分别显著降低51%至3.0±0.3 μM和63%至2.2±0.2 μM（P<0.05）。相比之下，L-丁硫氨酸-[S,R]-亚砜亚胺可使同型半胱氨酸浓度升高41%至8.6±0.6 μM（P<0.05）。对照组血浆中的谷胱甘肽浓度为19.5±1.9 μM，给予N-乙酰半胱氨酸后无变化。还原型谷胱甘肽可使血浆谷胱甘肽升高至379.7±22.9 μM（P<0.05），而L-丁硫氨酸-[S,R]-亚砜亚胺可使血浆谷胱甘肽浓度降至5.3±0.4 μM。同型半胱氨酸与血浆中的谷胱甘肽（r=-0.399，P<0.01）和半胱氨酸（r=-0.52，P<0.01）浓度呈负相关。我们的结论是，调节谷胱甘肽水平会影响大鼠血浆中的同型半胱氨酸浓度。
