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Valproic acid down‐regulates the conversion of arachidonic acid to eicosanoids via cyclooxygenase‐1 and ‐2 in rat brain
Author(s) -
Bosetti Francesca,
Weerasinghe Gayani R.,
Rosenberger Thad A.,
Rapoport Stanley I.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01701.x
Subject(s) - arachidonic acid , cyclooxygenase , valproic acid , chemistry , lipoxygenase , metabolite , pharmacology , prostaglandin , enzyme , leukotriene , endocrinology , lithium (medication) , medicine , hydroxyeicosatetraenoic acid , eicosanoid , arachidonate 5 lipoxygenase , biochemistry , epilepsy , psychiatry , asthma
Sodium valproate, a mood stabilizer, when chronically administered to rats (200 mg/kg i.p. daily for 30 days) significantly reduced the brain protein levels of cyclooxygenase (COX)‐1 and COX‐2, without altering the mRNA levels of these enzymes. COX activity was decreased, as were the brain concentrations of 11‐dehydrothromboxane B 2 and prostaglandin E 2 (PGE 2 ), metabolites of arachidonic acid (AA) produced via COX. In contrast, the brain protein level of 5‐lipoxygenase and the concentration of its AA metabolite leukotriene B 4 were unchanged. In view of published evidence that lithium chloride administered chronically to rats, like chronic valproate, reduces AA turnover within brain phospholipids, and that lithium post‐transcriptionally down‐regulates COX‐2 but not COX‐1 protein level and enzyme activity, these observations suggest that mood stabilizers generally modulate the release and recycling of AA within brain phospholipids, and the conversion of AA via COX‐2 to PGE 2 and related eicosanoids. If targeting this part of the ‘AA cascade’ accounts for their therapeutic action, non‐steroidal anti‐inflammatory drugs or selective COX‐2 inhibitors might prove effective in bipolar disorder.