Mood stabilizers / oxidative damage / lithium and valproate



Chronic treatment with mood stabilizers lithium and valproate prevents
excitotoxicity by inhibiting oxidative stress in rat cerebral cortical
cells.
Shao L, Young LT, **** JF
Biol Psychiatry. 2005 Dec 1; 58(11): 879-84

BACKGROUND:
Recent studies indicate that chronic treatment with the
mood-stabilizing drugs lithium and valproate produces a neuroprotective
effect against excitotoxicity.
In this study, we aimed to determine whether inhibiting oxidative
damage plays a role in a neuroprotective effect of lithium and
valproate against excitotoxicity.
METHODS:
Intracellular free calcium concentration was measured with the
fluorescent calcium ion indicator fluo-3. Malondialdehyde, an end
product derived from peroxidation of polyunsaturated fatty acid, and
protein carbonyls were used to assess oxidative damage to lipid and
protein. Excitotoxicity was assayed by measuring cell viability with
the MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]
method and by measuring deoxyribonucleic acid (DNA) fragmentation with
TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine
triphosphate nick end labeling) staining. RESULTS:
We found that chronic treatment with lithium and valproate at their
therapeutically relevant concentrations significantly inhibited the
glutamate-induced increase of intracellular free calcium concentration,
lipid peroxidation, protein oxidation, DNA fragmentation, and cell
death in primary cultured rat cerebral cortical cells.
This treatment had no effect on basal intracellular free calcium
concentration, lipid peroxidation, protein oxidation, DNA
fragmentation, and cell death.
CONCLUSIONS: Our results suggest that chronic treatment with lithium
and valproate inhibits oxidative damage to lipid and protein and in
turn produces a neuroprotective effect against excitotoxicity.


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