ABSTRACT
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. .
Subject(s)
Animals , Female , Mice , Alzheimer Disease/drug therapy , Estradiol/therapeutic use , Memory Disorders/drug therapy , Ovariectomy , Oxidative Stress/drug effects , Phytoestrogens/therapeutic use , Zeranol/analogs & derivatives , Blotting, Western , DNA Damage/drug effects , DNA Repair Enzymes/analysis , Hippocampus/drug effects , Immunohistochemistry , Phosphoric Monoester Hydrolases/analysis , Reproducibility of Results , Time Factors , Treatment Outcome , Zeranol/therapeutic useABSTRACT
Mycoestrogen zearalenone [ZEA] is found in human foods and animal feeds. Its estrogenic potency mainly depends on its biotransformation fate. The hepatic biotransformation of ZEA in rainbow trout was investigated in this study. Various concentrations of ZEA were separately incubated with the hepatic microsomal and post-mitochondrial sub-fractions in the presence of NADPH, and the metabolites were determined by means of HPLC. Moreover, the rate of glucuronidation for ZEA and its reduced metabolites were estimated in the presence of uridine diphosphate glucuronic acid. beta-zearalenol [beta-ZOL] was found to be the major metabolite of ZEA by both sub-cellular fractions. The enzymatic kinetics analyses indicated that the alpha-ZOL and beta-ZOL production by microsomal fraction were 8- and 2-fold higher than those by post-mitochondrial fraction, respectively. High percentages of ZEA and its metabolites are conjugated with glucuronic acid at the lower concentrations. Data suggest that the hepatic biotransformation of ZEA in rainbow trout resulted in its detoxification as the main metabolite tends to be beta-ZOL with weak estrogenic property. Moreover, at certain concentrations, the produced metabolites are entirely conjugated with glucuronic acid, which may consequently cause a prolonged duration of action due to entero-hepatic cycle