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Effects of mood stabilizers on DNA damage in an animal model of mania.

Abstract

OBJECTIVE

Recent studies have suggested that oxidative stress and DNA damage may play a role in the pathophysiology of bipolar disorder (BD). We investigated the effects of the mood stabilizers lithium and valproate on amphetamine-induced DNA damage in an animal model of mania and their correlation with oxidative stress markers.

METHODS

In the first experiment (reversal model), we treated adult male Wistar rats with D-amphetamine (AMPH) or saline for 14 days; between the 8th and 14th days, rats also received lithium, valproate or saline. In the second experiment (prevention model), rats received either lithium, valproate or saline for 14 days; between the 8th and 14th days, we added AMPH or saline. We evaluated DNA damage using single-cell gel electrophoresis (comet assay), and we assessed the mutagenic potential using the micronucleus test. We assessed oxidative stress levels by lipid peroxidation levels (TBARS) and antioxidant enzyme activities (superoxide dismutase and catalase). We assessed DNA damage and oxidative stress markers in blood/plasma and hippocampal samples. We evaluated mutagenesis in fresh lymphocytes.

RESULTS

In both models, we found that AMPH increased peripheral and hippocampal DNA damage. The index of DNA damage correlated positively with lipid peroxidation, whereas lithium and valproate were able to modulate the oxidative balance and prevent recent damage to the DNA. However, lithium and valproate were not able to prevent micronucleus formation.

CONCLUSION

Our results support the notion that lithium and valproate exert central and peripheral antioxidant-like properties. In addition, the protection to the integrity of DNA conferred by lithium seems to be limited to transient DNA damage and does not alter micronuclei formation.

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  • Authors+Show Affiliations

    ,

    Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Brazil.

    , , , , , , , , , , ,

    Source

    MeSH

    Amphetamine
    Animals
    Antimanic Agents
    Antioxidants
    Bipolar Disorder
    Central Nervous System Stimulants
    Comet Assay
    DNA Damage
    Hippocampus
    Lipid Peroxidation
    Lithium Chloride
    Male
    Micronucleus Tests
    Motor Activity
    Oxidative Stress
    Rats
    Rats, Wistar
    Valproic Acid

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    18982174

    Citation

    Andreazza, Ana Cristina, et al. "Effects of Mood Stabilizers On DNA Damage in an Animal Model of Mania." Journal of Psychiatry & Neuroscience : JPN, vol. 33, no. 6, 2008, pp. 516-24.
    Andreazza AC, Kauer-Sant'Anna M, Frey BN, et al. Effects of mood stabilizers on DNA damage in an animal model of mania. J Psychiatry Neurosci. 2008;33(6):516-24.
    Andreazza, A. C., Kauer-Sant'Anna, M., Frey, B. N., Stertz, L., Zanotto, C., Ribeiro, L., ... Kapczinski, F. (2008). Effects of mood stabilizers on DNA damage in an animal model of mania. Journal of Psychiatry & Neuroscience : JPN, 33(6), pp. 516-24.
    Andreazza AC, et al. Effects of Mood Stabilizers On DNA Damage in an Animal Model of Mania. J Psychiatry Neurosci. 2008;33(6):516-24. PubMed PMID: 18982174.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of mood stabilizers on DNA damage in an animal model of mania. AU - Andreazza,Ana Cristina, AU - Kauer-Sant'Anna,Marcia, AU - Frey,Benicio N, AU - Stertz,Laura, AU - Zanotto,Caroline, AU - Ribeiro,Leticia, AU - Giasson,Karine, AU - Valvassori,Samira S, AU - Réus,Gislaine Z, AU - Salvador,Mirian, AU - Quevedo,João, AU - Gonçalves,Carlos A, AU - Kapczinski,Flavio, PY - 2008/11/5/pubmed PY - 2009/2/21/medline PY - 2008/11/5/entrez KW - DNA damage KW - bipolar disorder KW - dopamine KW - lithium KW - models, animal KW - oxidative stress SP - 516 EP - 24 JF - Journal of psychiatry & neuroscience : JPN JO - J Psychiatry Neurosci VL - 33 IS - 6 N2 - OBJECTIVE: Recent studies have suggested that oxidative stress and DNA damage may play a role in the pathophysiology of bipolar disorder (BD). We investigated the effects of the mood stabilizers lithium and valproate on amphetamine-induced DNA damage in an animal model of mania and their correlation with oxidative stress markers. METHODS: In the first experiment (reversal model), we treated adult male Wistar rats with D-amphetamine (AMPH) or saline for 14 days; between the 8th and 14th days, rats also received lithium, valproate or saline. In the second experiment (prevention model), rats received either lithium, valproate or saline for 14 days; between the 8th and 14th days, we added AMPH or saline. We evaluated DNA damage using single-cell gel electrophoresis (comet assay), and we assessed the mutagenic potential using the micronucleus test. We assessed oxidative stress levels by lipid peroxidation levels (TBARS) and antioxidant enzyme activities (superoxide dismutase and catalase). We assessed DNA damage and oxidative stress markers in blood/plasma and hippocampal samples. We evaluated mutagenesis in fresh lymphocytes. RESULTS: In both models, we found that AMPH increased peripheral and hippocampal DNA damage. The index of DNA damage correlated positively with lipid peroxidation, whereas lithium and valproate were able to modulate the oxidative balance and prevent recent damage to the DNA. However, lithium and valproate were not able to prevent micronucleus formation. CONCLUSION: Our results support the notion that lithium and valproate exert central and peripheral antioxidant-like properties. In addition, the protection to the integrity of DNA conferred by lithium seems to be limited to transient DNA damage and does not alter micronuclei formation. SN - 1488-2434 UR - https://www.unboundmedicine.com/medline/citation/18982174/Effects_of_mood_stabilizers_on_DNA_damage_in_an_animal_model_of_mania_ L2 - http://www.jpn.ca/vol33-issue6/33-6-516/ DB - PRIME DP - Unbound Medicine ER -