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Chronic treatment with mood stabilizers lithium and valproate prevents excitotoxicity by inhibiting oxidative stress in rat cerebral cortical cells.
Biol Psychiatry. 2005 Dec 01; 58(11):879-84.BP

Abstract

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.

Authors+Show Affiliations

Shao L
The Vivian Rakoff Mood Disorders Laboratory, Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Ontario, Canada.
Young LT
No affiliation info available
Wang JF
No affiliation info available

MeSH

AnimalsAntimanic AgentsCalciumCell SurvivalCells, CulturedCerebral CortexExcitatory Amino AcidsGlutamic AcidIn Situ Nick-End LabelingLipid PeroxidationLithiumNerve Tissue ProteinsOxidation-ReductionOxidative StressRatsRats, Sprague-DawleyValproic Acid

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16005436

Citation

Shao, Li, et al. "Chronic Treatment With Mood Stabilizers Lithium and Valproate Prevents Excitotoxicity By Inhibiting Oxidative Stress in Rat Cerebral Cortical Cells." Biological Psychiatry, vol. 58, no. 11, 2005, pp. 879-84.
Shao L, Young LT, Wang JF. Chronic treatment with mood stabilizers lithium and valproate prevents excitotoxicity by inhibiting oxidative stress in rat cerebral cortical cells. Biol Psychiatry. 2005;58(11):879-84.
Shao, L., Young, L. T., & Wang, J. F. (2005). Chronic treatment with mood stabilizers lithium and valproate prevents excitotoxicity by inhibiting oxidative stress in rat cerebral cortical cells. Biological Psychiatry, 58(11), 879-84.
Shao L, Young LT, Wang JF. Chronic Treatment With Mood Stabilizers Lithium and Valproate Prevents Excitotoxicity By Inhibiting Oxidative Stress in Rat Cerebral Cortical Cells. Biol Psychiatry. 2005 Dec 1;58(11):879-84. PubMed PMID: 16005436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic treatment with mood stabilizers lithium and valproate prevents excitotoxicity by inhibiting oxidative stress in rat cerebral cortical cells. AU - Shao,Li, AU - Young,L Trevor, AU - Wang,Jun-Feng, Y1 - 2005/07/07/ PY - 2005/02/02/received PY - 2005/04/25/revised PY - 2005/04/28/accepted PY - 2005/7/12/pubmed PY - 2006/1/18/medline PY - 2005/7/12/entrez SP - 879 EP - 84 JF - Biological psychiatry JO - Biol Psychiatry VL - 58 IS - 11 N2 - 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. SN - 0006-3223 UR - https://www.unboundmedicine.com/medline/citation/16005436/Chronic_treatment_with_mood_stabilizers_lithium_and_valproate_prevents_excitotoxicity_by_inhibiting_oxidative_stress_in_rat_cerebral_cortical_cells_ DB - PRIME DP - Unbound Medicine ER -