The effects of valproate on the arachidonic acid metabolism of rat brain microvessels and of platelets

Zoltán Szupera, Zsófia Mezei, Béla Kis, Árpád Gecse, László Vécsei, Gyula Telegdy

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Long-term administration of the antiepileptic drug valproate can induce hematologic, hepatic and endocrine abnormalities and morphologic alterations in the brain capillaries and glial cells. Valproate elicits bone marrow suppression, reducing the number of red blood cells and platelets, and causes platelet functional abnormalities. Various data suggest that more than one mechanism of valproate-associated toxicity may exist, but the pathomechanism of cell function alterations elicited by valproate has not yet been elucidated. The reported ex vivo experiments were designed to investigate the effects of valproate on the arachidonic acid cascade of rat brain capillaries and platelets. Valproate was administered (300 mg/kg body weight/day) in the drinking water to male Wistar rats for 2 weeks. Isolated platelets and brain microvessels were labelled with [14C]arachidonic acid and the released [14C]eicosanoids were separated by overpressure thin-layer chromatography and determined quantitatively by liquid scintillation counting. Valproate treatment reduced the synthesis of cyclooxygenase and lipoxygenase products in rat platelets. In brain microvessels valproate stimulated the synthesis of lipoxygenase metabolites and attenuated the cyclooxygenase pathway. Modifications of the arachidonate cascade in platelets and brain microvessels may contribute to the cell function alterations caused by valproate. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)205-210
Number of pages6
JournalEuropean Journal of Pharmacology
Volume387
Issue number2
DOIs
Publication statusPublished - Jan 10 2000

Keywords

  • Arachidonic acid cascade
  • Brain microvessel
  • Platelet
  • Rat
  • Valproate

ASJC Scopus subject areas

  • Pharmacology

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