Valproate-induced stimulation of calcium uptake by isolated rat liver mitochondria

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Treatment with valproic acid (VPA) to control seizure has been associated with impaired mitochondrial structure and function. Previous studies showed enlarged mitochondrial matrix granules containing calcium in liver biopsies from epileptic children on the drug. We have now studied the effect of VPA on 45Ca2+-uptake in isolated rat liver mitochondria. Therapeutic and lower VPA concentrations stimulated 45Ca2+-uptake. VPA also induced a significant decline in mitochondrial glutathione (GSH) levels. The stimulation of 45Ca2+-uptake was inversely correlated with GSH levels (r = -0.91). Addition of GSH to the incubation medium where 45Ca2+-uptake was monitored in the presence of VPA reversed the stimulating effect of the drug. These findings suggest that the stimulation of 45Ca2+-uptake by VPA is due to the decrease in GSH mediated by the drug.

Original languageEnglish
Pages (from-to)777-779
Number of pages3
JournalMedical Science Research
Issue number11
StatePublished - 1998
Externally publishedYes


  • Calcium uptake
  • Glutathione
  • Mitochondria
  • Valproate


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