RESUMEN
AIM: The aim of this study was to evaluate the hepatic and circulating expression of miR-155, miR-122 and miR-217 in a model of chronic exposure to ethanol in adult zebrafish. METHODS: Wild-type adult zebrafish were divided into two groups (n = 281): an EG (exposed to 0.5% v/v Ethanol in aquarium water) and a CG (without ethanol). After 28 days the animals were euthanized, followed by histopathological analysis, quantification of lipids, triglycerides and inflammatory cytokines in liver tissue. miR-155, miR-122 and miR-217 gene expression was quantified in liver tissue and serum. RESULTS: We observed hepatic lesions and increased accumulation of hepatic lipids in the EG. The expression of il-1ß was higher in the EG, but there were no differences in il-10 and tnf-α between groups. In the liver, expression of miR-122 and miR-155 was higher in the EG. The circulating expression of miR-155 and miR-217 was significantly higher in the EG. CONCLUSION: Chronic exposure to ethanol in zebrafish leads to altered hepatic and circulating expression of miR-155, miR-122 and miR-217. This confirms its potential as a biomarker and therapeutic target.
Asunto(s)
Etanol/farmacología , Hepatopatías Alcohólicas/genética , Hígado/efectos de los fármacos , MicroARNs/genética , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Hígado/metabolismo , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/patología , Masculino , MicroARNs/metabolismo , Triglicéridos/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Pez CebraRESUMEN
The hepatoprotective effects of the ethanolic extracts of propolis (EEP) on alcohol-induced liver steatosis were investigated in Wistar rats. Chronic alcoholic fatty liver was induced by administration of 52% alcohol to male Wistar rats at the dose of 1% body weight for 7 weeks. Then animals were simultaneously treated with 50% ethanol solutions of EEP or normal saline at the dose of 0.1% body weight for 4 further weeks. Serological analyses and liver histopathology studies were performed to investigate the development of steatosis. Microarray analysis was conducted to investigate the alterations of hepatic gene expression profiling. Our results showed that 4-week treatment of EEP helped to restore the levels of various blood indices, liver function enzymes and the histopathology of liver tissue to normal levels. Results from the microarray analysis revealed that the hepatic expressions of genes involved in lipogenesis were significantly down-regulated by EEP treatment, while the transcriptional expressions of functional genes participating in fatty acids oxidation were markedly increased. The ability of EEP to reduce the negative effects of alcohol on liver makes propolis a potential natural product for the alternative treatment of alcoholic fatty liver.
Asunto(s)
Hígado Graso Alcohólico/metabolismo , Hepatopatías Alcohólicas/metabolismo , Extractos Vegetales/metabolismo , Própolis/metabolismo , Sustancias Protectoras/metabolismo , Alanina Transaminasa/metabolismo , Animales , Apiterapia/métodos , Aspartato Aminotransferasas/metabolismo , Colesterol/metabolismo , Modelos Animales de Enfermedad , Etanol , Ácidos Grasos/biosíntesis , Hígado Graso Alcohólico/tratamiento farmacológico , Hígado Graso Alcohólico/genética , Hígado Graso Alcohólico/patología , Hepatopatías Alcohólicas/tratamiento farmacológico , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/patología , Masculino , Oxidación-Reducción , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Própolis/química , Própolis/uso terapéutico , Sustancias Protectoras/química , Sustancias Protectoras/uso terapéutico , Ratas Wistar , Análisis de Matrices Tisulares/métodos , Transcripción Genética/genética , Triglicéridos/metabolismoRESUMEN
Alcoholic liver disease (ALD) is a definition encompassing a spectrum of disorders ranging from simple steatosis to cirrhosis and hepatocellular carcinoma. Excessive alcohol consumption triggers a series of metabolic reactions that affect the liver by inducing lipogenesis, increasing oxidative stress, and causing abnormal inflammatory responses. The metabolic pathways regulating lipids, reactive oxygen species (ROS), and immune system are closely related and in some cases cross-regulate each other. Therefore, it must be taken into account that major genetic and epigenetic abnormalities affecting enzymes involved in one of such pathways can play a pivotal role in ALD pathogenesis. However, recent studies have pointed out how a significant predisposition can also be determined by minor variants, such as relatively common polymorphisms, epigenetic modifications, and microRNA abnormalities. Genetic and epigenetic factors can also affect the progression of liver diseases, promoting fibrogenesis, cirrhosis, and ultimately hepatocellular carcinoma. It is noteworthy that some of these factors, such as some of the cytokines involved in the abnormal inflammatory responses, are shared with non-alcoholic liver disease, while other factors are unique to ALD. The study of the genetic and epigenetic components involved in the liver damages caused by alcohol is crucial to identify individuals with high risk of developing ALD, design personalized protocols for prevention and/or treatment, and select the best molecular targets for new therapies.
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Epigénesis Genética , Hepatopatías Alcohólicas/genética , Animales , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Inflamación/genética , Metabolismo de los Lípidos/genética , Hepatopatías Alcohólicas/diagnóstico , Hepatopatías Alcohólicas/inmunología , Hepatopatías Alcohólicas/metabolismo , MicroARNs/genética , Estrés Oxidativo/genética , Fenotipo , Pronóstico , Factores de Riesgo , Transducción de Señal/genéticaRESUMEN
This study evaluated the effect of green tea application time on the bond strength of enamel after enamel bleaching. Enamel samples were obtained from 80 third molars and randomly divided into 7 experimental groups (G1-G7) and 1 group without treatment (G8): G1, bleached with 10% carbamide peroxide (CP); G2, CP + 10% sodium ascorbate gel (SA) for 15 min; G3, CP + SA for 30 min; G4, CP + SA for 60 min; G5, CP + 10% green tea gel (GT) for 15 min; G6, CP + GT for 30 min; G7, CP + GT for 60 min. The CP was applied onto the enamel surface for 8 h for 14 days. The SA was applied in groups 2, 3 and 4, and the GT was applied in groups 5-8 according to the above described application times. Immediately after treatment, the specimens were bonded with Adper Single Bond 2 and Filtek Z350XT. The specimens were prepared to microtensile bond strength analysis. Fracture mode analysis was performed using a stereoscopic loupe. The data were statistically analyzed by two-way analysis of variance, the Tukey's and Dunnett's tests (=5%). The means (standard deviation) were: G1, 23.3 (3.2); G2, 25.2 (3.9); G3, 26.4 (5.4); G4, 30.2 (4.5); G5, 26.6 (3.4); G6, 22.0 (5.4); G7, 31.4 (3.3); G8, 31.4 (3.2). All groups had a high percentage of adhesive failures. In conclusion, the bond strength values were higher than the value in the bleached group only when the antioxidants were applied for 60 min.
Este estudo avaliou o efeito do tempo de aplicação do chá verde na resistência de união do esmalte após o clareamento. Amostras de esmalte foram obtidas a partir de 70 terceiros molares e aleatoriamente divididas em 7 grupos experimentais (G1-G7) e um grupo sem tratamento (G8). Os 7 grupos experimentais foram tratados como segue: G1, clareado com peróxido de carbamida a 10% (PC); G2, PC + gel de ascorbato de sódio a 10% (AS) por 15 min; G3, PC + AS por 30 min; G4, PC + AS por 60 min; G5, PC + gel de chá verde a 10% (CV) por 15 min; G6, PC + CV por 30 min; G7, PC + CV por 60 min. O PC foi aplicado na superfície do esmalte por 8 h, durante 14 dias. O AS foi aplicado nos grupos 2, 3 e 4 e o CV foi aplicado nos grupos 5, 6 e 7 de acordo com os tempos de aplicação descritos acima. Imediatamente após o tratamento, foi realizado o procedimento adesivo utilizando Adper Single Bond 2 e Filtek Z350XT. Em seguida, as amostras foram preparadas para o teste de microtração. A análise do padrão de fratura foi realizada em lupa estereoscópica. Os dados foram analisados através de ANOVA (2 fatores), testes de Tukey e Dunnett (α=5%). As médias (desvio padrão) foram: G1: 23,29 (3,20); G2: 25,18 (3,95); G3: 26,41 (5,40); G4: 30,17 (4,46); G5: 26,63 (3,43); G6: 22,02 (5,41); G7: 31,40 (3,35); G8: 31,4 (3,2). Todos os grupos apresentaram maior porcentagem de falhas adesivas. Em conclusão, os valores de resistência de união foram maiores que os dos grupos clareados somente quando os antioxidantes foram aplicados por 60 min.
Asunto(s)
Humanos , Masculino , Hepatopatías Alcohólicas/fisiopatología , ARN Mensajero/metabolismo , Factor de Crecimiento Transformador beta/genética , Hepatopatías Alcohólicas/genética , Factor de Crecimiento Transformador beta1 , Factor de Crecimiento Transformador beta/sangreRESUMEN
Alcoholism and cirrhosis, which are two of the most serious health problems worldwide, have a broad spectrum of clinical outcomes. Both diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each population. In contrast to other regions around the world, Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol consumption. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects. The Mexican population has an admixture genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another. Furthermore, they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver disease. Thus, in this era of genomics, personalized medicine will benefit patients if it is directed according to individual or population-based data. Additional association studies will be required to establish novel strategies for the prevention, care and treatment of liver disease in Mexico and worldwide.
Asunto(s)
Consumo de Bebidas Alcohólicas/etnología , Consumo de Bebidas Alcohólicas/genética , Alcoholismo/etnología , Alcoholismo/genética , Interacción Gen-Ambiente , Hepatopatías Alcohólicas/etnología , Hepatopatías Alcohólicas/genética , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/mortalidad , Bebidas Alcohólicas , Alcoholismo/mortalidad , Características Culturales , Predisposición Genética a la Enfermedad , Herencia , Humanos , Hepatopatías Alcohólicas/mortalidad , México/epidemiología , Linaje , Pronóstico , Factores de Riesgo , Conducta SocialRESUMEN
CONTEXT: Alcoholic liver disease (ALD) is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE) gene mutations and the severity of liver disease in alcoholic patients. OBJECTIVES: To compare the prevalence of mutations in the hemochromatosis (HFE) gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. METHODS: Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment) and 52 healthy controls (during elective cholecystectomy). All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations). Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. RESULTS: ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05), but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI): 2.09-142.34, P = 0.008). However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003). CONCLUSION: s ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no detectable effects on liver disease activity or severity.
Asunto(s)
Antígenos de Histocompatibilidad Clase I/genética , Sobrecarga de Hierro/patología , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/patología , Proteínas de la Membrana/genética , Estudios de Casos y Controles , Femenino , Genotipo , Proteína de la Hemocromatosis , Humanos , Sobrecarga de Hierro/genética , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
Context Alcoholic liver disease (ALD) is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE) gene mutations and the severity of liver disease in alcoholic patients. Objectives To compare the prevalence of mutations in the hemochromatosis (HFE) gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment) and 52 healthy controls (during elective cholecystectomy). All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations). Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05), but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI): 2.09-142.34, P = 0.008). However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003). Conclusions ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, ...
Contexto A doença hepática alcoólica (DHA) está geralmente associada à sobrecarga de ferro, que pode contribuir para a sua patogênese, através do aumento do estresse oxidativo e dano celular. As descrições existentes na literatura sobre a associação entre mutações HFE e a gravidade da DHA nem sempre são concordantes. Objetivos Comparar a prevalência de mutações HFE entre um grupo de pacientes com DHA e uma população de controle. Avaliar a relação entre mutações HFE e os depósitos de ferro hepático. Avaliar se a presença dessas mutações está associada com a gravidade da DHA. Métodos Compararam-se 63 pacientes com DHA que efetuaram biopsia hepática com 52 controles saudáveis. A genotipagem HFE (wild type, C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M, W164X) e uma avaliação laboratorial de rotina (incluindo cinética do ferro) foram feitos em todos os indivíduos. Realizou-se regressão logística multivariada nos casos para avaliar se a presença de mutações HFE estava relacionada com risco aumentado de depósitos de ferro hepático aumentados, ferritina sérica anormal, fibrose hepática significativa ou atividade necroinflamatória. Resultados Os pacientes apresentaram ferritina sérica e saturação da transferrina mais elevadas que os controles, mas não existiram diferenças significativas na distribuição de mutações HFE entre pacientes e controles. Considerando apenas os pacientes, o risco relativo de estes apresentarem pelo menos uma mutação HFE e depósitos de ferro hepático significativos foi de 17.23 (CI 95% 2.09-142.34, P = 0.008). Contudo, a presença ...
Asunto(s)
Femenino , Humanos , Masculino , Persona de Mediana Edad , Antígenos de Histocompatibilidad Clase I/genética , Sobrecarga de Hierro/patología , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/patología , Proteínas de la Membrana/genética , Estudios de Casos y Controles , Genotipo , Sobrecarga de Hierro/genética , Índice de Severidad de la EnfermedadRESUMEN
Treatment of alcoholic liver disease is for the most part based on the stage of the disease and the pathogenic event that is being targeted. The primary treatment modalities that are considered in the treatment of alcoholic liver disease include abstinence, agents that suppress inflammation, anticytokine therapy, nutritional support, modifiers of alcohol metabolism, anti-oxidants, and inhibitors of hepatic fibrosis. Future therapeutic options include exploration of new pathways such as the patatin-like phospholipase domain containing 3 protein (PNPLA-3).
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Hepatopatías Alcohólicas/terapia , Templanza , Alcoholismo/genética , Alcoholismo/patología , Alcoholismo/terapia , Animales , Antiinflamatorios/uso terapéutico , Manejo de la Enfermedad , Terapia Genética/tendencias , Humanos , Lipasa/genética , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/patología , Proteínas de la Membrana/genética , Apoyo Nutricional/métodosRESUMEN
Alcohol use disorders and alcohol dependency affect millions of individuals worldwide. The impact of these facts lies in the elevated social and economic costs. Alcoholic liver disease is caused by acute and chronic exposure to ethanol which promotes oxidative stress and inflammatory response. Chronic consumption of ethanol implies liver steatosis, which is the first morphological change in the liver, followed by liver fibrosis and cirrhosis. This review comprises a broad approach of alcohol use disorders, and a more specific assessment of the pathophysiologic molecular basis, and genetics, as well as clinical presentation and current modalities of treatment for alcoholic liver disease.
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Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/terapia , Causas de Muerte , Humanos , Hepatopatías Alcohólicas/mortalidad , Organización Mundial de la SaludRESUMEN
Although in the past several mechanisms and factors have been proposed to be responsible for alcoholic liver disease (ALD), at present the involvement of oxygen free radicals and consequently of oxidative stress has acquired remarkable credit. In numerous experimental studies it has been shown the occurrence of alcohol-induced generation of oxygen- and ethanol-derived free radicals through different pathways and from different sources. Mitochondria appear to be both an important source of reactive oxygen species (ROS) and also a primary target of ethanol-induced damage. The consistent induction of the mitochondrial antioxidant enzyme manganese superoxide dismutase (Mn-SOD) observed in experimental animals after acute and chronic ethanol administration has all the characteristics of a "stress response" to an oxidative insult.
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Antioxidantes/fisiología , Etanol/efectos adversos , Estrés Oxidativo/fisiología , Animales , Humanos , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/fisiopatología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/fisiologíaRESUMEN
Although the interaction between alcohol and the liver has been the subject of intensive investigation since many years, several uncertainties remain to be solved. Good examples of what we need to learn are: The real number of patients with alcohol-induced liver disease (AILD), the dose of alcohol "safe" for the liver, the genetic predisposition to the damage or, on the other side of the coin, protecting from the damage. Rather recently, however, part of these questions started to be clarified, thus permitting a better definition of the role of each of these factors in AILD. In parallel to the clinical approach to AILD, the unveiling of the molecular and biochemical mechanisms involved in AILD has progressed and proved to be important in both a better understanding of the disease and, more important, in a more rational treatment of these disorders. This review will focus on what we currently know of AILD in clinical, biochemical and molecular terms and what we need to address in the future.
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Hepatopatías Alcohólicas/fisiopatología , Animales , Femenino , Humanos , Cirrosis Hepática Alcohólica/genética , Cirrosis Hepática Alcohólica/fisiopatología , Cirrosis Hepática Alcohólica/terapia , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/terapia , Modelos Animales , Ratas , Factores de RiesgoRESUMEN
Although the interaction between alcohol and the liver has been the subject of intensive investigation since many years, several uncertainties remain to be solved. Good examples of what we need to learn are: The real number of patients with alcohol-induced liver disease (AILD), the dose of alcohol "safe" for the liver, the genetic predisposition to the damage or, on the other side of the coin, protecting from the damage. Rather recently, however, part of these questions started to be clarified, thus permitting a better definition of the role of each of these factors in AILD. In parallel to the clinical approach to AILD, the unveiling of the molecular and biochemical mechanisms involved in AILD has progressed and proved to be important in both a better understanding of the disease and, more important, in a more rational treatment of these disorders. This review will focus on what we currently know of AILD in clinical, biochemical and molecular terms and what we need to address in the future
Asunto(s)
Humanos , Animales , Ratas , Etanol , Hepatopatías Alcohólicas/etiología , Alcohol Deshidrogenasa , Factor de Necrosis Tumoral alfa , Etanol , Estrés Oxidativo , Hepatopatías Alcohólicas/genéticaRESUMEN
In the recent past, major achievements have been obtained in the understanding of the molecular defects at the basis of several different diseases. The field of 'Molecular Medicine' has thus become more solid, and several reports have been published linking the basic molecular investigation to the clinical practice. In line with this new approach to medicine a Symposium was organized where the linkage between investigations in basic science could be explored in view of clinical disorders, and vice versa. in Rosario, Argentina, September 9-11, 1999, molecular biologists, molecular pathologists and clinicians discussed the molecular defects possibly at the basis of some common diseases. This report summarizes the presentations and discussions during the symposium.
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Arteriosclerosis/genética , Bilirrubina/metabolismo , VIH/genética , Hepacivirus/fisiología , Hepatopatías Alcohólicas/genética , Hígado Artificial , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/terapia , Arteriosclerosis/inmunología , Hepatitis C/terapia , Humanos , Hepatopatías Alcohólicas/inmunología , Hepatopatías Alcohólicas/metabolismoRESUMEN
A sample of 30 alcoholic patients, selected according to a rigorous criterion, was compared with two samples of the general population with respect to the distribution of HLA antigens. The sole inclusion criterion was the presence of signs and symptoms of an alcohol withdrawal syndrome. The alcoholic sample did not differ from the general population sample with respect to ABO blood group distribution, and had minimal evidence of alcoholic liver disease. The alcoholic group showed highly significant differences from the two general population samples with respect to the HLA system, consisting of a much higher frequency of HLA B40 and DR4 antigens and a much lower frequency of DR3. The results are consistent with the view that alcoholism may have a precise genetic determination.