RESUMO
OBJECTIVE: The aim of this study was to evaluate the effect of a novel phytoestrogen, α-Zearalanol, on Alzheimer's disease-related memory impairment and neuronal oxidation in ovariectomized mice. METHODS: Female C57/BL6 mice were ovariectomized or received sham operations and treatment with equivalent doses of 17ß-estradiol or α-Zearalanol for 8 weeks. Their spatial learning and memory were analyzed using the Morris water maze test. The antioxidant enzyme activities and reactive oxygen species generation, neuronal DNA oxidation, and MutT homolog 1 expression in the hippocampus were measured. RESULTS: Treatment with 17ß-estradiol or α-Zearalanol significantly improved spatial learning and memory performance in ovariectomized mice. In addition, 17ß-estradiol and α-Zearalanol attenuated the decrease in antioxidant enzyme activities and increased reactive oxygen species production in ovariectomized mice. The findings indicated a significant elevation in hippocampi neuronal DNA oxidation and reduction in MutT homolog 1 expression in estrogen-deficient mice, but supplementation with 17ß-estradiol or α-Zearalanol efficaciously ameliorated this situation. CONCLUSION: These results demonstrate that α-Zearalanol is potentially beneficial for improving memory impairments and neuronal oxidation damage in a manner similar to that of 17ß-estradiol. Therefore, the compound may be a potential therapeutic agent that can ameliorate neurodegenerative disorders related to estrogen deficiency.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Estradiol/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Fitoestrógenos/uso terapêutico , Zeranol/análogos & derivados , Animais , Western Blotting , Dano ao DNA/efeitos dos fármacos , Enzimas Reparadoras do DNA/análise , Feminino , Hipocampo/efeitos dos fármacos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Monoéster Fosfórico Hidrolases/análise , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Zeranol/uso terapêuticoRESUMO
OBJECTIVE: The aim of this study was to evaluate the effect of a novel phytoestrogen, α-Zearalanol, on Alzheimer's disease-related memory impairment and neuronal oxidation in ovariectomized mice. METHODS: Female C57/BL6 mice were ovariectomized or received sham operations and treatment with equivalent doses of 17β-estradiol or α-Zearalanol for 8 weeks. Their spatial learning and memory were analyzed using the Morris water maze test. The antioxidant enzyme activities and reactive oxygen species generation, neuronal DNA oxidation, and MutT homolog 1 expression in the hippocampus were measured. RESULTS: Treatment with 17β-estradiol or α-Zearalanol significantly improved spatial learning and memory performance in ovariectomized mice. In addition, 17β-estradiol and α-Zearalanol attenuated the decrease in antioxidant enzyme activities and increased reactive oxygen species production in ovariectomized mice. The findings indicated a significant elevation in hippocampi neuronal DNA oxidation and reduction in MutT homolog 1 expression in estrogen-deficient mice, but supplementation with 17β-estradiol or α-Zearalanol efficaciously ameliorated this situation. CONCLUSION: These results demonstrate that α-Zearalanol is potentially beneficial for improving memory impairments and neuronal oxidation damage in a manner similar to that of 17β-estradiol. Therefore, the compound may be a potential therapeutic agent that can ameliorate neurodegenerative disorders related to estrogen deficiency. .