| Title | Glutathione reductase is inhibited by acetaminophen-glutathione conjugate in vitro. | | Author(s) | Roušar T, Pařík P, Kučera O, Bartoš M, Cervinková Z | | Institution | Department of Physiology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic. Tomas.Rousar@upce.cz. | | Source | Physiol Res 2009 Jun 19. | | Abstract | The aim of the present work was to investigate a new mechanism likely contributing to the toxic action of acetaminophen especially to explore the possible inhibition of glutathione reductase through an acetaminophen-glutathione conjugate (APAP-SG). APAP-SG conjugate was synthesized by organic synthesis and purified by column chromatography. The inhibitory effect of the conjugate on two types of glutathione reductase (from yeasts and rat hepatocytes) was tested spectrophotometrically. We found that the enzyme activity was reduced similarly after treatment with 2.96 mM acetaminophen-glutathione conjugate in both yeast and hepatocyte glutathione reductases (GR); the enzyme activity was inhibited to 52.7 +/- 1.5 % (2.4 +/- 0.3 mU/ml) in yeast GR (control activity was 5.6 +/- 0.3 mU/ml) and to 48.1 +/- 8.8 % (2.2 +/- 0.2 mU/ml) in rat hepatocytes lysate GR (control activity was 5.2 +/- 0.2 mU/ml). In addition, the enzyme activity (from hepatocytes lysate) was decreased to 79+/-7 %, 67+/-2 % and 39+/-7 %, in 0.37, 1.48 and 3.7 mM concentration of the conjugate, respectively. We found that glutathione reductase, the essential enzyme of the antioxidant system, was dose-dependently inhibited by the product of acetaminophen metabolism - the conjugate of acetaminophen and glutathione. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19537930 |
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