The effects of vigabatrin on rat liver antioxidant status

Drug Metabol Drug Interact. 2005;21(2):109-15. doi: 10.1515/dmdi.2005.21.2.109.

Abstract

The anti-epileptic drug vigabatrin was developed as an inhibitor of gamma-aminobutyric acid transaminase, and its ability to increase inhibition in the central nervous system led to its testing in an animal model. In animal models chronic use of vigabatrin is associated with irreversible myelin vacuolation. Antioxidant drugs change the antioxidant capacity of the body. Oxidative stress of the body increased when valproic acid and carbamazepine were used chronically. To assess whether vigabatrin may affect protein oxidation and lipid peroxidation, glutathione, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) levels were studied in the livers of 57 rat fetuses after administration of vigabatrin to the mothers (19 in the first week of pregnancy, 20 in the second week, and 18 in the third week) and in 19 control rat fetuses without vigabatrin. We compared the results of administration of vigabatrin in each group with the controls. Rat fetus protein oxidation in group I (0.686 nmol/mg protein) and group II (0.723 nmol/mg protein) was higher than in the control group (0.388 nmol/mg protein). Lipid peroxidation (0.209, 0.224, 0.253 nmol/mg protein, respectively) and GPx levels (345.4, 329.0, 283.2 nmol/mg protein, respectively) of groups I, II, and III were higher than in the control group (0.104, 167.2 nmol/mg protein, respectively). GST in group II (79.2 nmol/mg protein) and group III (77.8 nmol/mg protein) were not different from that in the control group (78 nmol/mg protein). It was found that vigabatrin affected all the parameters that were studied, especially in group I, which was given the drug in the first week of pregnancy.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Antioxidants / analysis*
  • Female
  • Gestational Age
  • Glutathione / analysis
  • Glutathione Peroxidase / analysis
  • Glutathione Transferase / analysis
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / enzymology
  • Maternal-Fetal Exchange*
  • Pregnancy
  • Proteins / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Spectrophotometry
  • Vigabatrin / pharmacology*

Substances

  • Anticonvulsants
  • Antioxidants
  • Proteins
  • Glutathione Peroxidase
  • Glutathione Transferase
  • Glutathione
  • Vigabatrin