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

      1 ,
      Pharmacology & toxicology
      Wiley

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          Abstract

          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.

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          Author and article information

          Journal
          Pharmacol Toxicol
          Pharmacology & toxicology
          Wiley
          0901-9928
          0901-9928
          Sep 2000
          : 87
          : 3
          Affiliations
          [1 ] Department of Surgery, University of Bergen, Haukeland University Hospital, Norway. Kjell.Ovrebo@kir.uib.no
          Article
          10.1111/j.0901-9928.2000.870301.x
          11068849
          6f8c99f3-6178-49fc-8dd3-93921db50be0
          History

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