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
Subject(s)
Oxidation-Reduction , Oncorhynchus mykiss , Biotransformation , Subcellular Fractions , Zeranol/analogs & derivativesABSTRACT
A high affinity polyclonal antibody-based enzyme linked immunosorbent assay (ELISA) was developed for the quantification of zeranol in bovine urine. On the basis of urine matrix studies, the optimized dilution factors producing insignificant matrix interference were selected as 1:5 in pretreatment. In the improved ELISA, the linear response range was between 0.02 and 1 microg/ml, and the detection limit was 0.02 microg/ml for the assay. The overall recoveries and the coefficients of variation (CVs) were in the range of 82% to approximately 127% and 3.5% to approximately 8.8%, respectively. Thirty-six bovine urine samples spiked with zeranol (ranging from 0.2 to 10 microg/ml) were detected by the ELISA and liquid chromatography (LC) method, and good correlations were obtained between the two methods (R(2)=0.9643). We conclude that this improved ELISA is suitable tool for a mass zeranol screening and can be an alternative for the conventional LC method for zeranol in bovine urine.
Subject(s)
Animals , Cattle , Calibration , Chromatography, High Pressure Liquid , Enzyme-Linked Immunosorbent Assay , Methods , Indicator Dilution Techniques , Zeranol , Allergy and Immunology , UrineABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of alpha-zearalenol on angiotensin II-induced beta3 integrin mRNA expression in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>The mRNA level in integrin beta3 was determined by reverse transcription-polymerase chain reaction. Endothelial NF-kappaB activity was determined by the luciferase activity assay of plasmid NF-kappaB-LUC.</p><p><b>RESULTS</b>The angiotensin II-induced beta3 integrin mRNA expression was inhibited by alpha-zearalenol and 17beta-estradiol (10 nmol/L -1 micromol/L), but not influenced by ICI 182, 780, a pure competitive antagonist for estrogen receptor or a nitric oxide inhibitor Nomega-Nitro-L-arginine methyl ester hydrochloride. Alpha-zearalenol and 17beta-estradiol suppressed the angiotensin II-induced activation of NF-kappaB in endothelial cells.</p><p><b>CONCLUSION</b>Alpha-zearalenol inhibits angiotensin II-induced integrin beta3 mRNA expression by suppressing NF-kappaB activation in endothelial cells.</p>
Subject(s)
Female , Humans , Angiotensin II , Cells, Cultured , Endothelial Cells , Metabolism , Endothelium, Vascular , Metabolism , Estradiol , Pharmacology , Gene Expression Regulation , Integrin beta3 , Genetics , NF-kappa B , Physiology , Nitric Oxide , Phytoestrogens , Pharmacology , RNA, Messenger , Metabolism , Receptors, Estrogen , Zeranol , PharmacologyABSTRACT
Utilizaram-se 40 bezerros Holandês x Zebu com objetivo de avaliar a viabilidade econômica da utilização do colostro fermentado, do óleo de soja e do zeranol em bezerros entre o 15º e o 60º dia de vida. Diariamente, foram fornecidos 1,5kg de concentrado contendo 23 por cento de proteína bruta, feno de tifton (Cynodon dactylon) à vontade e três litros de leite ou colostro fermentado. Considerando as despesas de criação e as receitas geradas, verificou-se menor custo dos animais tratados com colostro fermentado. Esse resultado, associado ao bom desempenho obtido, demonstrou que o colostro fermentado é eficiente como substituto do leite para bezerros em fase de aleitamento, gerando maior lucratividade.
Subject(s)
Animals , Cattle , Colostrum , Economics , Diet , Soybean Oil , ZeranolABSTRACT
Utilizaram-se 40 bezerros Holandês I Zebu distribuídos em oito tratamentos (T): leite integral (1); leite integral com óleo de soja (2); leite integral e zeranol (3); leite integral com óleo de soja e zeranol (4); colostro fermentado (5); colostro fermentado com óleo de soja (6); colostro fermentado e zeranol (7); e colostro fermentado com óleo de soja e zeranol (8) com o objetivo de avaliar o consumo de alimentos, o crescimento e a conversão alimentar de animais entre o 15º e o 60º dia de vida. Diariamente, foram fornecidos 1,5kg de concentrado contendo 23 por cento de proteína bruta, feno de tifton (Cynodon dactylon) à vontade e três litros de leite ou colostro fermentado. O colostro fermentado proporcionou melhores resultados de peso corporal e ganho de peso quando comparado ao leite integral, mas semelhantes aos resultados com zeranol. Também promoveu maior ingestão de matéria seca em relação ao leite integral, o que resultou em desempenhos semelhantes para esses dois tipos de alimento. Não houve diferenças entre os tratamentos quanto aos componentes não-integrantes da carcaça. O tratamento com leite e zeranol resultou em maior peso de carne industrial e o com óleo de soja aumentou a proporção de gordura interna. O colostro fermentado é uma boa opção para a recria de machos leiteiros e o efeito do zeranol sobre o ganho de peso é dependente da dieta dos animais.
Subject(s)
Animals , Cattle , Colostrum , Diet , ZeranolABSTRACT
<p><b>OBJECTIVE</b>To study the effects of phytoestrogen alpha-zearalanol (alpha-ZAL) on normal human breast.</p><p><b>METHODS</b>Ten specimens of normal human breast tissues were subcutaneously implanted into 30 athymic nude mice aged 9-10 weeks, one for 3 mice. These mice were then randomly divided into three groups: control group (without hormone treatment, n = 10), 1 mg/kg alpha-ZAL group (n = 10), and 5 mg/kg alpha-ZAL group (n = 10). All breast tissues were taken out 6 weeks later. Immunohistochemistry was used to determine the protein expressions of proliferating cell nuclear antigen (PCNA), inhibiting apoptosis gene Bcl-2, estrogen receptor (ER), and progesterone receptor (PR). Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expression levels of estrogen sulfotransferase (EST) mRNA and bridging integrator protein-1 (BIN1) mRNA. Morphological features of grafts before and after treatment were also observed.</p><p><b>RESULTS</b>Alpha-ZAL had no significant effects on Bcl-2, PCNA, ER, and PR expression of mammary epithelial cells in graft specimens. Alpha-ZAL upregulated BIN1 mRNA expression in grafts, but had no significant effect on ESTmRNA expression.</p><p><b>CONCLUSIONS</b>Alpha-ZAL does not affect the morphology, proliferating, and apoptosis of epithelial cells in normal human breast tissues implanted into nude mice, but it may increase the gene expression of tumor-inhibiting BIN1, suggesting that alpha-ZAL may have potential proteotive effect on normal human breast.</p>
Subject(s)
Adult , Animals , Female , Humans , Mice , Breast , Chemistry , Estrogens, Non-Steroidal , Pharmacology , Mice, Inbred BALB C , Mice, Nude , Phytoestrogens , Pharmacology , Proliferating Cell Nuclear Antigen , Random Allocation , Receptors, Estrogen , Receptors, Progesterone , Zeranol , PharmacologyABSTRACT
El propósito del presente estudio fue evaluar el efecto del zeranol sobre la estructura histológica del útero de chinchillas implantadas con este compuesto por vía subcutánea a dosis de 12 mg/animal. Se utilizaron 30 chinchillas con las que se formaron dos grupos, uno de hembras vírgenes de 12 a 15 meses de edad y otro de hembras adultas de 24 a 30 meses de edad, con partos previos. Cada uno de estos grupos tuvo su respectivo testigo. Los animales fueron sacrificados y se obtuvieron fragmentos de útero para efectuar su evaluación histológica. En los animales implantados, de ambas edades, los hallazgos más relevantes fueron aumento de dos a tres veces las dimensiones del útero (determinado en campos microscópicos), congestión vascular en la lámina propia y en el miometrio. Asimismo, se observaron células epiteliales en mitosis o apoptosis en los animales implantados de 12 a 15 meses de edad, mientras que en las hembras con edad de 24 a 30 meses se identificaron de cuatro a cinco veces más células mitóticas o apoptóticas, respectivamente, en las hembras implantadas en relación con las no implantadas; se cuantificó un mayor número de glándulas endometriales en la mayoría de los animales implantados de ambas edades. En el endometrio de los animales no implantados no se observó congestión vascular y sólo en 20 por ciento de los animales de 24 a 30 meses de edad se observó mitosis o apoptosis. Estos resultados demuestran que el zeranol a dosis de 12 mg/ animal induce en el útero de las chinchillas jóvenes y adultas, cambios en los ámbitos vascular y tisular, característicos de un estado estrogénico predominante.
Subject(s)
Animals , Zeranol , Chinchilla , Uterus , EndometriumABSTRACT
Con el objeto de evaluar el efecto de la lactona del ácido resorcílico (zeranol) sobre la maduración de la piel de chinchilla, se realizó un experimento en un diseño completamente al azar por grupo de edad y sexo. El estudio duró 4 meses en la época de verano-otoño (junio-septiembre). Se incluyeron 33 hembras vírgenes de 12 a 24 meses de edad, 60 machos de 12 a 18 meses; y 29 hembras en producción de 24 a 48 meses de edad; a la mitad de los animales se les implantó subcutáneamente 12 mg de zeranol. La evaluación visual se hizo cada 2 semanas y se obtuvieron las pieles cuando las 3 franjas del color del pelo presentaban el mismo nivel en toda la superficie del cuerpo, momento en el cual se considera como piel madura. Se realizó un análisis de sobrevida mediante el método de Log Rank ajustado por grupos, en el cual se encontró un efecto anagénico significativo (P< 0.01) del zeranol. El porcentaje de maduración en los animales implantados fue 84 por ciento, 94 por ciento y 50 por ciento en los machos, hembras jóvenes y hembras adultas, respectivamente; mientras que para los no tratados la maduración fue de 20 por ciento, 38 por ciento y 13.3 por ciento, para los mismos grupos. Se hicieron dos análisis de Log Rank ajustado por grupos de tratamiento, los cuales mostraron un efecto de edad y sexo; en ambos casos las hembras jóvenes presentaron un mayor porcentaje de maduración que las hembras adultas y que los machos (P< 0.01)