RESUMO
Epigenetic regulation of imprinted genes is regarded as a highly plausible explanation for linking dietary exposures in early life with the onset of diseases during childhood and adulthood. We sought to test whether prenatal dietary supplementation with docosahexaenoic acid (DHA) during pregnancy may modulate epigenetic states at birth. This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg of DHA or a placebo from gestation week 18-22 to parturition. We applied quantitative profiling of DNA methylation states at IGF2 promoter 3 (IGF2 P3), IGF2 differentially methylated region (DMR), and H19 DMR in cord blood mononuclear cells of the DHA-supplemented group (n = 131) and the control group (n = 130). In stratified analyses, DNA methylation levels in IGF2 P3 were significantly higher in the DHA group than the control group in preterm infants (P = 0.04). We also observed a positive association between DNA methylation levels and maternal body mass index; IGF2 DMR methylation was higher in the DHA group than the control group in infants of overweight mothers (P = 0.03). In addition, at H19 DMR, methylation levels were significantly lower in the DHA group than the control group in infants of normal weight mothers (P = 0.01). Finally, methylation levels at IGF2/H19 imprinted regions were associated with maternal BMI. These findings suggest that epigenetic mechanisms may be modulated by DHA, with potential impacts on child growth and development.
Assuntos
Peso ao Nascer/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Fator de Crescimento Insulin-Like II/genética , RNA Longo não Codificante/genética , Adulto , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Modelos Lineares , Masculino , Análise Multivariada , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Regiões Promotoras Genéticas/genéticaRESUMO
BACKGROUND: Korean red ginseng (KRG) is a processed ginseng from raw ginseng to enhance safety, preservation and efficacy, known having beneficial effects on women's health due to its estrogen like function. While estrogen supplementation showed some modulation of endocrine disrupting chemicals, bisphenol A (BPA) has been focused as a potential endocrine disrupting chemical. In this study, we examined the efficacy and safety outcomes of KRG against BPA, focusing on female quality of life (QOL). Individual variations in susceptibility to KRG were also investigated with the Sasang Typology, the personalized medicine used for hundred years in Korea. METHODS: We performed a single-blind randomized clinical trial. Study subjects were young women (N = 22), consumed 2.7 g of KRG or placebo per day for 2 weeks and filled up questionnaires regarding gynecologic complaints at the 4 time spots. We analyzed urinary total BPA and malondialdehyde (MDA), an oxidative stress biomarker, with GC/MS and HPLC/UVD respectively, and diagnosed their Sasang Typology with the questionnaire for the Sasang constitution Classification (QSCC II). RESULTS: KRG consumption decreased urinary BPA and MDA levels (ps < 0.05) and alleviated 'menstrual irregularity', 'menstrual pain', and 'constipation' (ps < 0.05). SoEum type (Lesser Yin person) among the Sasang types showed significant alleviation in insomnia, flushing, perspiration and appetite by KRG consumption, rather than other Sasang types. During the intervention, no one experienced any aggravated side effects. CONCLUSION: We suggest KRG is efficient for protection for female QOL and BPA- exposure and - related oxidative stress. However, individual variation in susceptibility to KRG should be further considered for identifying ideal therapy. TRIAL REGISTRATION: KCT0000920.
Assuntos
Compostos Benzidrílicos/urina , Distúrbios Menstruais/tratamento farmacológico , Distúrbios Menstruais/urina , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Fenóis/urina , Extratos Vegetais/farmacologia , Adulto , Análise de Variância , Feminino , Humanos , Malondialdeído/urina , Medicina Tradicional Coreana , República da Coreia , Método Simples-Cego , Adulto JovemRESUMO
Epigenetic changes have been implicated in virtually all types of human malignancies. In contrast to genetic changes, epigenetic changes occur in a gradual manner during the tumorigenic process and they are potentially reversible. Because epigenetic changes have frequently been detected in high-risk populations, they are attractive targets to prevent the initiation of premalignant lesions or their advance to a malignant stage. A wide range of chemical entities has been found capable of altering the epigenome in animal models and humans. Epidemiological and laboratory-based studies suggested that these agents may have an anti-neoplastic effect against different cancer types. Several of these agents have been tested as dietary supplements, often with conflicting results. In this review, we discuss recent developments in our understanding of agents capable of modulating the epigenome and their potential to prevent human cancer when administered as dietary supplements.
Assuntos
Anticarcinógenos/uso terapêutico , Biomarcadores Tumorais/genética , Suplementos Nutricionais , Epigênese Genética/efeitos dos fármacos , Neoplasias/prevenção & controle , Animais , Biomarcadores Tumorais/metabolismo , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Metilação de DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , MicroRNAs/metabolismo , Neoplasias/epidemiologia , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Fatores de RiscoRESUMO
BACKGROUND: Early-life exposures to tobacco smoke and some dietary factors have been identified to induce epigenetic changes in genes involved in allergy and asthma development. Omega-3 (n-3) polyunsaturated fatty acid (PUFA) intake during pregnancy could modulate key cytokines and T helper (Th) cell maturation; however, little is known about the mechanism by which ω-3 PUFA could have a beneficial effect in preventing inflammatory disorders. OBJECTIVE: We sought to test whether prenatal dietary supplementation with ω-3 PUFA during pregnancy may modulate epigenetic states in the infant immune system. DESIGN: This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg docosahexaenoic acid (DHA) or a placebo from 18 to 22 wk of gestation to parturition. We applied quantitative profiling of DNA methylation states in Th1, Th2, Th17, and regulatory T-relevant genes as well as LINE1 repetitive elements of cord blood mononuclear cells (n = 261). RESULTS: No significant difference in promoter methylation levels was shown between ω-3 PUFA-supplemented and control groups for the genes analyzed; however, ω-3 PUFA supplementation was associated with changes in methylation levels in LINE1 repetitive elements (P = 0.03) in infants of mothers who smoked during pregnancy. Furthermore, an association between the promoter methylation levels of IFNγ and IL13 was modulated by ω-3 PUFA supplementation (P = 0.06). CONCLUSIONS: Our results indicate that maternal supplementation with ω-3 PUFA during pregnancy may modulate global methylation levels and the Th1/Th2 balance in infants. Therefore, the epigenetic mechanisms could provide attractive targets for prenatal modulation and prevention of inflammatory disorders and potentially other related diseases in childhood and adulthood.
Assuntos
Metilação de DNA/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Sistema Imunitário/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Pré-Natal , Adolescente , Adulto , Método Duplo-Cego , Epigênese Genética , Ácidos Graxos Ômega-3/sangue , Feminino , Humanos , Lactente , Interferon gama/sangue , Interferon gama/genética , Interleucina-13/sangue , Interleucina-13/genética , Modelos Lineares , México , Análise Multivariada , Gravidez , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Equilíbrio Th1-Th2/efeitos dos fármacos , Adulto JovemRESUMO
Korean pear (Pyrus pyrifolia cv. Shingo) has been used as a traditional medicine for alleviating alcohol hangover. However, scientific evidence for its effectiveness or mechanism is not clearly established. To investigate its mechanism of alcohol detoxification, both in vitro and in vivo studies were performed with an aldehyde dehydrogenase 2 (ALDH2) alternated animal model. The pear extract (10 mL/kg bw) was administered to Aldh2 normal (C57BL/6) and deficient (Aldh2 -/-) male mice. After 30 min, ethanol (1 g or 2 g/kg bw) was administered to the mice via gavage. Levels of alcohol and acetaldehyde in blood were quantified by GC/MS. First, it was observed that the pears stimulated both alcohol dehydrogenase (ADH) and ALDH activities by 2â¼3- and 1.3-fold in in vitro studies, respectively. Second, mouse PK data (AUC(∞) and C(max) ) showed that the pear extract decreased the alcohol level in blood regardless of ALDH2 genotype. Third, the pear increased the acetaldehyde level in blood in Aldh2 deficient mice but not in Aldh2 normal mice. Therefore, the consistent in vitro and in vivo data suggest that Korean pears stimulate the two key alcohol-metabolizing enzymes. These stimulations could be the main mechanism of the Korean pear for alcohol detoxification. Finally, the results suggest that polymorphisms of human ALDH2 could bring out individual variations in the effects of Korean pear on alcohol detoxification.
Assuntos
Aldeído Desidrogenase/metabolismo , Etanol/sangue , Inativação Metabólica , Extratos Vegetais/farmacologia , Pyrus/química , Acetaldeído/sangue , Álcool Desidrogenase/metabolismo , Aldeído-Desidrogenase Mitocondrial , Animais , Etanol/toxicidade , Genótipo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
For health of future generation, fertile young women should be monitored for exposure of endocrine disrupting chemicals (EDCs). Among EDCs, bisphenol A (BPA) is suggested to induce reactive oxygen species (ROS) which play an important role in pathologies of female diseases such as endometriosis. On the other hand, previous studies suggested that sprouts of wheat (Triticum aestivum) have antimutagenicity and antioxidant activity. We performed the 2 weeks intervention of wheat sprout juice (100ml/day) to investigate its effects on BPA-exposure and -oxidative toxicity in young women (N=14, age=24.4±4.0). Geometrical mean of urinary BPA levels was 1.81 (GSTD, 4.34)µg/g creatinine. We observed that irregular meals significantly increased levels of urinary BPA approximate 3 times (p=0.03). In addition, we found BPA-induced oxidative stress is correlated with levels of 8-hydroxydeoxyguanosine (8-OHdG) or malondialdehyde (MDA) levels (p=0.18 or 0.03, respectively). We also observed a continuous reduction of urinary BPA during the wheat sprout intervention (p=0.02). In summary, our data suggested potential detoxification of wheat sprouts on BPA-toxicity via antioxidative and interference of absorption, distribution, metabolism and excretion (ADME)-mediated mechanisms in young women.
Assuntos
Antioxidantes/farmacologia , Disruptores Endócrinos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Triticum/química , Compostos Benzidrílicos , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Fenóis/antagonistas & inibidores , Fenóis/urina , Espécies Reativas de Oxigênio/metabolismo , Adulto JovemRESUMO
Unlike mammals, avian cochlear hair cells can regenerate after acoustic overstimulation. The WDR1 gene is one of the genes suspected to play an important role in this difference. In an earlier study, we found that the WDR1 gene is over-expressed in the chick cochlea after acoustic overstimulation. The aim of this study was to compare the expression of WDR1 before and after acoustic overstimulation in the chick vestibule. Seven-day-old chicks were divided into three groups: normal group, damage group, and regeneration group. The damage and regeneration group was exposed to 120 dB SPL white noise for 5-6 hours. The damage group was euthanized shortly after the impulse, but the regeneration group was allowed to recover for 2 days. The utricle, saccule, and the three ampullae of each semicircular canal were dissected and immunohistochemically stained with anti-WD40 repeat protein 1 antibody. For quantitative analysis, immunoreactive densities were measured and quantitative real-time RT PCR was performed. WD40 repeat protein 1 expression was elevated in all the semicircular canals and utricle, two days after an acoustic overstimulation (P=0.001). WDR1 mRNA expression was 1.34 times higher in the regeneration group compared to the normal group, but it was not statistically significant. Exceptionally, WD40 repeat protein 1 expression did not increase in the saccule of the regeneration group. Elevated WDR1 expression in the avian vestibule may have a role in the hair cell regenerating ability as in the avian cochlea. A similar mechanism of hair cell regeneration may exist in the avian cochlea and vestibule.