No evidence for inhibition of human glutathione reductase by valproic acid.
The human red blood cell enzyme glutathione reductase (GR) was reported to be inhibited by the anticonvulsant drug valproic acid (VPA) [Cotariu et al., Biochem Pharmacol 43: 425-429, 1992]. When attempting to reproduce and extend these experiments, we could not detect any significant effect of VPA on glutathione reductase in haemolysates from 20 healthy children and 10 children under VPA therapy, no matter which concentration of the drug (0.9 or 1.8 mM in a haemolysate diluted by a factor of 50 or 1.8 mM directly in the assay), which incubation time (0-60 min) and which assay system were chosen. An influence of VPA on FAD-free apoglutathione reductase was also excluded. GR-activities of 10 children under VPA therapy (1.08 +/- 0.14 U/mL blood or 7.57 +/- 0.94 U/g Hb) were almost identical with the activities of age- and sex-matched controls (1.04 +/- 0.17 U/mL or 7.79 +/- 1.32 U/g Hb). No correlation between erythrocyte GR activity and serum levels of VPA was observed. Finally, incubation of crystalline human GR with VPA did not lead to enzyme inhibition; rather, in most experiments the enzyme was stabilized by incubation with VPA. Possible explanations for the discrepancies between the results of Cotariu et al. and our data are discussed.
Nordhoff
A
A
Institute of Biochemistry II, Heidelberg University, Germany.
Schirmer
R H
RH
Mayatepek
E
E
Becker
K
K
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004795:Enzyme Stability; D004912:Erythrocytes / Q000201:enzymology*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors*; D006801:Humans; D007223:Infant; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D014635:Valproic Acid; D005980:Glutathione Reductase