Effects of Memantine, a Non-Competitive N-Methyl-d-Aspartate Receptor Antagonist, on Genomic Stability

Authors

  • Édina Madeira Flores,

    1. Laboratório de Genética Toxicológica, Programa de Pós-Graduação em Genética e Toxicologia Aplicada, ULBRA, Canoas, RS, Brazil
    2. Laboratório de Farmacologia e Toxicologia, Programa de Pós-Graduação em Genética e Toxicologia Aplicada, ULBRA, Canoas, RS, Brazil
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  • Shandale Emanuele Cappelari,

    1. Laboratório de Genética Toxicológica, Programa de Pós-Graduação em Genética e Toxicologia Aplicada, ULBRA, Canoas, RS, Brazil
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  • Patrícia Pereira,

    1. Laboratório de Farmacologia e Toxicologia, Programa de Pós-Graduação em Genética e Toxicologia Aplicada, ULBRA, Canoas, RS, Brazil
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  • Jaqueline Nascimento Picada

    1. Laboratório de Genética Toxicológica, Programa de Pós-Graduação em Genética e Toxicologia Aplicada, ULBRA, Canoas, RS, Brazil
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Author for correspondence: Jaqueline Nascimento Picada, Laboratório de Genética Toxicológica, ULBRA: Avenida Farroupilha 8001, Bairro São José, CEP 92425-900, Canoas, RS, Brazil (fax +55 51 34771313, e-mail jnpicada@cpovo.net).

Abstract

Abstract:  Memantine is an aminoadamantane drug useful in neurodegenerative diseases, with beneficial effects on cognitive functions. Some studies have shown that memantine protects brain cells, thereby decreasing glutamate excitotoxicity. This study evaluated the genotoxic/antigenotoxic and mutagenic effects of memantine in CF-1 mice, following standardized protocols. Memantine was administered i.p. at 7.5, 15 or 30 mg/kg for three consecutive days. Blood and brain samples were collected to assess DNA damage using the alkaline comet assay. The mutagenic effect was assessed using the bone marrow micronucleus test. In addition, possible antioxidant effects were evaluated measuring the survival of Saccharomyces cerevisiae yeast strains [wild-type (WT) and isogenic mutants lacking superoxide dismutase] to cotreatment of memantine plus hydrogen peroxide. Memantine decreased DNA oxidative damage mainly in brain tissue. This antigenotoxic effect corroborated an increase observed in the survival of S. cerevisiae WT strain against hydrogen peroxide-induced damage. Furthermore, memantine did not increase the micronucleus frequency. The overall results indicate that memantine showed no mutagenic activity, did not cause DNA damage in the blood and brain tissues and showed antigenotoxic effects in brain tissue.

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