Cited by 160Bipolar Disorder and TreatmentGlutathione Transferases and PolymorphismsAntioxidant Activity and Oxidative Stress

Role of glutathione in neuroprotective effects of mood stabilizing drugs lithium and valproate

Cui, J., Shao, L., Young, L.T., Wang, J.-F.·2007·Neuroscience

Abstract

Mood stabilizing drugs lithium and valproate are the most commonly used treatments for bipolar disorder. Previous studies in our laboratory indicate that chronic treatment with lithium and valproate inhibits oxidative damage in primary cultured rat cerebral cortical cells. Glutathione, as the major antioxidant in the brain, plays a key role in defending against oxidative damage. The purpose of this study was to determine the role of glutathione in the neuroprotective effects of lithium and valproate against oxidative damage. We found that chronic treatment with lithium and valproate inhibited reactive oxygen metabolite H(2)O(2)-induced cell death in primary cultured rat cerebral cortical cells, while buthionine sulfoximine, an inhibitor of glutathione rate-limiting synthesis enzyme glutamate-cysteine ligase, reduced the neuroprotective effect of lithium and valproate against H(2)O(2)-induced cell death. Further, we found that chronic treatment with lithium and valproate increased glutathione levels in primary cultured rat cerebral cortical cells and that the effects of lithium and valproate on glutathione levels were dose-dependent in human neuroblastoma SH-SY5Y cells. Chronic treatment with lithium and valproate also increased the expression of glutamate-cysteine ligase in both rat cerebral cortical cells and SH-SY5Y cells. In addition, chronic treatment with other mood stabilizing drugs lamotrigine and carbamazepine, but not antidepressants desipramine and fluoxetine, increased both glutathione levels and the expression of glutamate-cysteine ligase in SH-SY5Y cells. These results suggest that glutathione plays an important role in the neuroprotective effects of lithium and valproate, and that glutathione may be a common target for mood stabilizing drugs.

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Crossref · 10.1016/j.neuroscience.2006.11.010

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Authors
Cui, J., Shao, L., Young, L. T., & Wang, J.-F.
Affiliations
Centre for Addiction and Mental Health (CA)
Corresponding author
Wang, J.-F.
Venue
Neuroscience
Publisher
Elsevier BV
Published
2007-02
Volume
144
Issue
4
Pages
1447-1453
ISSN
0306-4522 (ISSN-L)
OpenAlex
W2085156996
Cited by
160
References
54
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 11 · 2014: 13 · 2013: 9 · 2012: 20
FWCI
7.21
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
glutathione, neuroprotection, mood stabilizers, lithium, valproic acid, bipolar disorder, oxidative stress, gamma-glutamylcysteine synthetase, buthionine sulfoximine, hydrogen peroxide-induced cell death, SH-SY5Y cells, lamotrigine, carbamazepine, glutathione synthesis
MeSH terms
Lamotrigine, Animals, Brain, Carbamazepine, Cells, Cultured, Cerebral Cortex, Enzyme Inhibitors, Glutamate-Cysteine Ligase, Glutathione, Humans, Lithium, Nerve Degeneration, Neurons, Triazines, Valproic Acid, Cell Death, Rats, Sprague-Dawley, Reactive Oxygen Species, Oxidative Stress, Antimanic Agents, Neuroprotective Agents, Cell Line, Tumor, Rats

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