RESUMO
Overexpression of the inducible isoform of the enzyme nitric oxide synthase (iNOS) has been associated to pathological processes in the kidney. Ethanol consumption induces the renal expression of iNOS; however, the contribution of this enzyme to the deleterious effects of ethanol in the kidney remains elusive. We examined whether iNOS plays a role in the renal dysfunction and oxidative stress induced by ethanol consumption. With this purpose, male C57BL/6 wild-type (WT) or iNOS-deficient (iNOS-/-) mice were treated with ethanol (20% v/v) for 10 weeks. Treatment with ethanol increased the expression of Nox4 as well as the concentration of thiobarbituric acid reactive substances and the levels of tumor necrosis factor α in the renal cortex of WT but not iNOS-/- mice. Augmented serum levels of creatinine and increased systolic blood pressure were found in WT and iNOS-/- mice treated with ethanol. WT mice treated with ethanol showed increased production of reactive oxygen species and myeloperoxidase activity, but these responses were attenuated in iNOS-/- mice. We concluded that iNOS played a role in ethanol-induced oxidative stress and pro-inflammatory cytokine production in the kidney. These are mechanisms that may contribute to the renal toxicity induced by ethanol.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Citocinas/metabolismo , Etanol/farmacologia , Inflamação/patologia , Nefropatias/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/patologia , Animais , Anti-Infecciosos Locais/toxicidade , Creatinina/metabolismo , Inflamação/enzimologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Nefropatias/etiologia , Nefropatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/biossíntese , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Binge drinking is the consumption of large volumes of alcohol in short periods and exerts its effects on the central nervous system, including the hippocampus. We have previously shown that binge drinking alters mitochondrial dynamics and induces neuroinflammation in the hippocampus of adolescent rats. Mild traumatic brain injury (mTBI), is regularly linked to alcohol consumption and share mechanisms of brain damage. In this context, we hypothesized that adolescent binge drinking could prime the development of brain damage generated by mTBI. We found that alcohol binge drinking induced by the "drinking in the dark" (DID) paradigm increases oxidative damage and astrocyte activation in the hippocampus of adolescent mice. Interestingly, adolescent animals submitted to DID showed decreased levels of mitofusin 2 that controls mitochondrial dynamics. When mTBI was evaluated as a second challenge, hippocampi from animals previously submitted to DID showed a reduction in dendritic spine number and a different spine profile. Mitochondrial performance could be compromised by alterations in mitochondrial fission in DID-mTBI animals. These data suggest that adolescent alcohol consumption can modify the progression of mTBI pathophysiology. We propose that mitochondrial impairment and oxidative damage could act as priming factors, modifying predisposition against mTBI effects.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/fisiopatologia , Lesões Encefálicas Traumáticas/fisiopatologia , Hipocampo/fisiopatologia , Maturidade Sexual/fisiologia , Consumo de Bebidas Alcoólicas/patologia , Animais , Consumo Excessivo de Bebidas Alcoólicas/complicações , Consumo Excessivo de Bebidas Alcoólicas/patologia , Consumo Excessivo de Bebidas Alcoólicas/fisiopatologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Espinhas Dendríticas/patologia , Modelos Animais de Doenças , Hipocampo/patologia , Inflamação/etiologia , Inflamação/patologia , Inflamação/fisiopatologia , Peroxidação de Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/fisiologia , Estresse OxidativoRESUMO
Oxidative stress is pointed out as a major mechanism by which ethanol induces functional and structural changes in distinctive tissues. We evaluated whether ethanol consumption would increase oxidative stress and cause micturition dysfunction. Male C57BL/6J mice were treated with 20% ethanol (v/v) for 10 weeks. Our findings showed that chronic ethanol consumption reduced micturition spots and urinary volume in conscious mice, whereas in anaesthetized animals cystometric analysis revealed reduced basal pressure and increased capacity, threshold pressure, and maximum voiding. Treatment with ethanol reduced the contraction induced by carbachol in isolated bladders. Chronic ethanol consumption increased the levels of oxidant molecules and thiobarbituric acid reactive species in the mouse bladder. Upregulation of Nox2 was detected in the bladder of ethanol-treated mice. Increased activity of both superoxide dismutase and catalase were detected in the mouse bladder after treatment with ethanol. Conversely, decreased levels of reduced glutathione were detected in the bladder of ethanol-treated mice. The present study first demonstrated that chronic ethanol consumption induced micturition dysfunction and that this response was accompanied by increased levels of oxidant molecules in the mousebladder. These findings suggest that ethanol consumption is a risk factor for vesical dysfunction.
Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Estresse Oxidativo , Bexiga Urinária/fisiopatologia , Micção , Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/patologia , Animais , Peso Corporal , Catalase/metabolismo , Regulação Enzimológica da Expressão Gênica , Glutationa/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Tamanho do Órgão , Oxirredução , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo , Bexiga Urinária/patologiaRESUMO
We evaluated the effects of ethanol consumption on the mitogen-activated protein kinases (MAPK) and metalloproteinases (MMP) pathways in the rat cavernosal smooth muscle (CSM). Male Wistar rats were treated with ethanol (20% v/v) for 6 weeks. Quantitative real-time polymerase chain reaction experiments showed that ethanol consumption did not alter mRNA levels of p38MAPK, SAPK/JNK, ERK1/2, MMP-2, or MMP-9 in the rat CSM. Western immunoblotting experiments revealed decreased protein expression of p38MAPK and phosphorylation of SAPK/JNK in the CSM from ethanol-treated rats. Additionally, ethanol consumption decreased the expression of MMP-2. Functional assays showed that SP600125, an inhibitor of SAPK/JNK, prevented the increase in endothelin (ET)-1-induced contraction in the CSM from ethanol-treated rats. Treatment with ethanol decreased MMP-2 activity, but did not change net MMP activity in the rat CSM. Ethanol consumption increased the circulating levels of MMP-2, MMP-9, and TIMP-2 as well as the MMP-9/TIMP-1 ratio. The major finding of our study is that ethanol consumption down-regulates both MAPK and MMP pathways in the rat CSM, whereas it increases the circulating levels of MMP-9. Additionally, we found that SAPK/JNK plays a role in ethanol-induced increase on ET-1 contraction in the isolated rat CSM.
Assuntos
Etanol/farmacologia , Metaloproteinases da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/patologia , Animais , Endotelina-1/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Metaloproteinases da Matriz/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos WistarRESUMO
Alcohol use disorder (AUD) is a complex multifactorial disease with heritability of â¼50% and corresponds to the state in which the body triggers a reinforcement or reward compulsive behavior due to ethanol consumption, even when faced with negative consequences. Although several studies have shown the impact of high ethanol intake on the prefrontal cortex (PFC) gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with relapsing. In this study, we used a chronic three-bottle free-choice mouse model to investigate the PFC transcriptome in three different groups of mice drinkers: 'Light drinkers' (preference for water throughout the experiment); 'Heavy drinkers' (preference for ethanol with a non-compulsive intake), and 'Inflexible drinkers' (preference for ethanol with a compulsive drinking component). Our aim was to correlate the intake patterns observed in this model with gene expression changes in the PFC, a brain region critical for the development and maintenance of alcohol addiction. We found that the Camk2a gene showed a downregulated profile only in the Inflexible when compared to the Light drinkers group, the Camk2n1 and Pkp2 genes showed an upregulated profile only in the Inflexible drinkers when compared to the Control group, and the Gja1 gene showed an upregulated profile in the Light and Inflexible drinkers when compared to the Control group. These different transcription patterns have been associated to the presence of alcohol, in the Camk2n1 and Gja1 genes; to the amount of ethanol consumed, in the Camk2a gene; and to the loss of control in the alcohol consumption, in the Pkp2 gene. Here, we provide, for the first time, the potential involvement of the Pkp2 gene in the compulsivity and loss of control over the voluntary ethanol consumption.
Assuntos
Consumo de Bebidas Alcoólicas/patologia , Alcoolismo/patologia , Alcoolismo/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Consumo de Bebidas Alcoólicas/fisiopatologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Modelos Animais de Doenças , Etanol/toxicidade , Masculino , Camundongos , Placofilinas/genética , Placofilinas/metabolismo , Córtex Pré-Frontal/efeitos dos fármacosRESUMO
Perigestational alcohol consumption by CF-1 mouse, from before mating up to the period of embryo organogenesis, leads to retarded early embryo development and neural tube defects. Here, we addressed if perigestational alcohol ingestion up to Day 10 of pregnancy induces oxidative stress and changes in macromolecules and organ tissues of early organogenic embryos. Adult CF-1 female mice were administered 10% ethanol in their drinking water for 17 days prior to mating and until Day 10 of gestation, whereas control females were administered ethanol-free water. Our results demonstrated significantly reduced Catalase abundance and activity and increased glutathione content in the embryos of ethanol-treated females. The nitrite level was significantly reduced, but TBARS (thiobarbituric acid reactive substances) content, an index of lipid peroxidation, did not change. Embryos derived from ethanol-treated females also showed higher abundance of 3-nitrotyrosine (3-NT)-containing proteins in all tissues, compared to the control group. Apoptosis was significantly increased in the ectoderm and mesoderm, but not in the heart-although this organ did contain more cleaved Caspase-3-positive cardiomyocytes per area of ventricular myocardium than controls. In sum, moderate perigestational alcohol ingestion up to Day 10 of gestation in mice induces oxidative stress by altering radical nitrogen species and antioxidant enzymatic and non-enzymatic mechanisms in embryos. Further, generalized protein nitration, due to unbalanced nitric oxide levels associated with tissue-specific apoptosis, was detected in embryos, suggesting that oxidative mechanisms may play an important role in the perigestational alcohol-induced malformation of organogenic embryos exposed to ethanol.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Apoptose/efeitos dos fármacos , Embrião de Mamíferos/efeitos dos fármacos , Etanol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/patologia , Animais , Animais não Endogâmicos , Antioxidantes/metabolismo , Dano ao DNA/efeitos dos fármacos , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/genética , Etanol/efeitos adversos , Feminino , Camundongos , Organogênese/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologiaRESUMO
Anxiety disorders are more likely to occur in women than in men, usually emerge during adolescence and exhibit high comorbidity with alcohol use disorders (AUD). Adolescents with high levels of anxiety or heightened reactivity to stress may be at-risk for developing AUD. An approach to analyze if high levels of inborn anxiety predict greater ethanol drinking is to assess the latter variable in subjects classified as high- or low-anxiety responders. The present study assessed ethanol drinking in adolescent, female Wistar, rats classified as high-, low- or average-anxiety responders and exposed or not to restraint stress (RS, Exp. 1). Classification was made through a multivariate index derived from testing anxiety responses in an elevated plus maze and a light-dark box tests. RS was applied after animals had been initiated to ethanol drinking. Intake of sweetened ethanol was unaffected by level of anxiety response. Adolescents with high levels of inborn anxiety exhibited significantly higher intake of unsweetened ethanol than counterparts with standard levels of anxiety, yet this effect was inhibited by RS exposure. Experiment 2 assessed FOS immunoreactivity after RS. Stress induced a significant increase in FOS immunoreactivity at the paraventricular nucleus, yet this effect was unaffected by level of anxiety response. Female adolescents with high levels of basal anxiety may be at-risk for exhibiting increased predisposition for ethanol intake and preference. The study also indicates that stress may exert differential effects on adolescent ethanol intake as a function of the level of anxiety response.
Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Ansiedade , Estresse Psicológico , Consumo de Bebidas Alcoólicas/patologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/patologia , Animais , Ansiedade/patologia , Ansiedade/fisiopatologia , Núcleo Arqueado do Hipotálamo/metabolismo , Núcleo Arqueado do Hipotálamo/patologia , Depressores do Sistema Nervoso Central/administração & dosagem , Modelos Animais de Doenças , Etanol/administração & dosagem , Feminino , Predisposição Genética para Doença , Análise Multivariada , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/patologia , Personalidade , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Restrição Física , Autoadministração , Maturidade Sexual , Estresse Psicológico/patologia , Estresse Psicológico/fisiopatologiaRESUMO
We described the effects of low- and high-dose ethanol intake on the structure and apoptosis signaling of the uterine endometrium of UChA and UChB rats (animals with voluntary ethanol consumption). Thirty adult female rats, 90 days old, were divided into three groups (n = 10/group): UChA rats fed with 10% (v/v) ethanol ad libitum (free choice for water or ethanol) drinking < 1.9 g/kg/day; UChB rats fed with 10% (v/v) ethanol ad libitum (free choice for water or ethanol) drinking from 2 to 5 g/kg/day; control rats without ethanol (only water). After 120 days of treatment, rats displaying estrus were euthanized. Uterine epithelial cells of the UCh rats showed dilated cisterns of the rough endoplasmic reticulum, presence of lipid droplets, altered nuclear chromatin, and disrupted mitochondria. The UCh rats exhibited intense atrophied epithelial cells with smaller areas and perimeters of cytoplasm and nuclei. The endometrium of UChA rats showed higher levels of caspase-3 while Xiap and Bcl2 varied from moderate to weak. Both UChA and UChB rats exhibited a stronger immunoreaction to Ki-67 and IGFR-1 on epithelial and stromal cells. Chronic ethanol intake leads to structural and molecular alterations in the uterine endometrium of UCh rats, regardless of low- or high-dose consumption, promoting reproductive disorders.
Assuntos
Consumo de Bebidas Alcoólicas/patologia , Endométrio/efeitos dos fármacos , Endométrio/patologia , Etanol/toxicidade , Consumo de Bebidas Alcoólicas/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Endométrio/ultraestrutura , Etanol/administração & dosagem , Feminino , RatosRESUMO
UNLABELLED: Background and rationale for the study. We designed to test whether there is interaction of maternal separation (MS) on the ethanol-preferring rats liver structure. The UCh rat pups were separated daily from their mothers during the stress hyporesponsive period (SHRP), between four and 14 days-old, always at the same time for four hours in a cage containing eight subdivisions, one for each pup. Subsequently, rats that presented the highest (UChB) and the lowest (UChA) ethanol (EtOH) consumption were selected to the study. Both UChB and UChA rats received 10% (v/v) EtOH and distilled water ad libitum until the end of the experiment (120 days-old). The liver was collected to histological routine for morphometric and stereological analyses, and immunohistochemistry. RESULTS: There was an interaction of MS and EtOH on the liver: increased liver mass, peritubular vessels, stellate cell numbers, steatosis and cell death, decreased necrosis, sinusoidal capillary diameters and cell proliferation. While there was a decrease in FSH, testosterone and 5α-di-hidrotestosterone, and increasing corticosterone and cholesterol. CONCLUSIONS: There is interaction of MS and EtOH on the liver structure, dependent on the amount of EtOH intake. Furthermore, the interaction of stress and drugs can increase or decrease their effects on the liver or indirectly via hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Ansiedade de Separação/patologia , Etanol/toxicidade , Hepatopatias Alcoólicas/etiologia , Fígado/efeitos dos fármacos , Fatores Etários , Consumo de Bebidas Alcoólicas/patologia , Animais , Animais Recém-Nascidos , Ansiedade de Separação/sangue , Ansiedade de Separação/psicologia , Biomarcadores/sangue , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Etanol/administração & dosagem , Fígado Gorduroso Alcoólico/etiologia , Fígado Gorduroso Alcoólico/patologia , Feminino , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/patologia , Hepatomegalia/induzido quimicamente , Hepatomegalia/patologia , Fígado/patologia , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/psicologia , Masculino , Fatores de TempoRESUMO
Alcohol use and misuse is known to involve structural brain changes. Numerous imaging studies have examined changes in gray matter (GM) volumes in dependent drinkers, but there is little information on whether non-dependent drinking is associated with structural changes and whether these changes are related to psychological factors-such as alcohol expectancy-that influence drinking behavior. We used voxel-based morphometry (VBM) to examine whether the global positive scale of alcohol expectancy, as measured by the Alcohol Expectancy Questionnaire-3, is associated with specific structural markers and whether such markers are associated with drinking behavior in 113 adult non-dependent drinkers (66 women). Alcohol expectancy is positively correlated with GM volume of left precentral gyrus (PCG) in men and women combined and bilateral superior frontal gyri (SFG) in women, and negatively correlated with GM volume of the right ventral putamen in men. Furthermore, mediation analyses showed that the GM volume of PCG mediate the correlation of alcohol expectancy and the average number of drinks consumed per occasion and monthly total number of drinks in the past year. When recent drinking was directly accounted for in multiple regressions, GM volume of bilateral dorsolateral prefrontal cortices correlated positively with alcohol expectancy in the combined sample. To our knowledge, these results are the first to identify the structural brain correlates of alcohol expectancy and its mediation of drinking behaviors. These findings suggest that more studies are needed to investigate increased GM volume in the frontal cortices as a neural correlate of alcohol expectancy.
Assuntos
Consumo de Bebidas Alcoólicas/patologia , Antecipação Psicológica/fisiologia , Lobo Frontal/patologia , Substância Cinzenta/patologia , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Caracteres SexuaisRESUMO
OBJECTIVE: To compare the frequency of micronuclei and metanucleated anomalies in the oral mucosa of smokers, alcoholic smokers, and nonsmokers. STUDY DESIGN: Three groups were studied: group I, 15 smokers; group II, 16 alcoholic smokers; and group III, 20 nonsmokers. Three smears from the lateral left border of the tongue were processed for Feulgen staining. A minimum of 300 cells per participant were examined for the quantification of micronuclei and metanucleated anomalies. RESULTS: The Kruskal-Wallis test showed no significant difference in the frequency of micronuclei (p = 0.602) or karyorrhexis (p = 0.114) among the three groups, but there was a significant difference in the frequency of broken eggs, binucleated cells, and karyolysis (p = 0.001). Spearman's correlation indicated an influence of the number of cigarettes per day on micronuclei frequency. Tobacco caused significant alterations in the exfoliative cytology (broken eggs, binucleated cells, and karyolysis) of chronic smokers, but not in the frequency of micronuclei or karyorrhexis, despite the observation of a larger absolute number of micronuclei in group II. CONCLUSION: The action of genotoxic agents (tobacco and alcohol) causes alterations in the frequency of micronuclei and metanucleated anomalies.
Assuntos
Consumo de Bebidas Alcoólicas/patologia , Mucosa Bucal/patologia , Fumar/patologia , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Feminino , Humanos , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Fumar/efeitos adversosRESUMO
The frequency of micronuclei in both buccal cells and peripheral blood lymphocytes is extensively used as a biomarker of chromosomal damage and genome stability in human populations. We examined whether prolonged exposure to complex mixtures of pesticides leads to an increase in cytogenetic damage. The exposed group comprised 50 agricultural aviators, mainly from Central and Southeast regions of Brazil, who had inhaled agrochemicals for more than 10 years without personal protection equipment; the control group consisted of 17 men from the same regions, without indication of exposure to pesticides, There were three times higher frequencies of micronuclei (P < 0.05) and 2.5 times higher frequencies of binucleated cells in the aviators when compared to controls. However, cytotoxic alterations such as broken eggs and karyorrhexis did not present statistically significant differences between the exposed and control groups. Therefore, diverse agrochemicals used to combat pests in agriculture possess genotoxic effects in the oral mucosa of the agricultural pilots, as showed in this study.
Assuntos
Agroquímicos/toxicidade , Aviação , Análise Citogenética , Dano ao DNA , Epitélio/patologia , Mucosa Bucal/patologia , Exposição Ocupacional/análise , Adulto , Consumo de Bebidas Alcoólicas/patologia , Brasil , Epitélio/efeitos dos fármacos , Humanos , Masculino , FumarRESUMO
BACKGROUND: Maternal alcohol use during pregnancy causes a continuum of long-lasting disabilities in the offspring, commonly referred to as fetal alcohol spectrum disorder (FASD). Attention-deficit/hyperactivity disorder (ADHD) is possibly the most common behavioral problem in children with FASD and devising strategies that ameliorate this condition has great clinical relevance. Studies in rodent models of ADHD and FASD suggest that impairments in the cAMP signaling cascade contribute to the hyperactivity phenotype. In this work, we investigated whether the cAMP levels are affected in a long-lasting manner by ethanol exposure during the third trimester equivalent period of human gestation and whether the acute administration of the PDE1 inhibitor vinpocetine ameliorates the ethanol-induced hyperactivity. METHODS: From postnatal day (P) 2 to P8, Swiss mice either received ethanol (5g/kg i.p.) or saline every other day. At P30, the animals either received vinpocetine (20mg/kg or 10mg/kg i.p.) or vehicle 4h before being tested in the open field. After the test, frontal cerebral cortices and hippocampi were dissected and collected for assessment of cAMP levels. RESULTS: Early alcohol exposure significantly increased locomotor activity in the open field and reduced cAMP levels in the hippocampus. The acute treatment of ethanol-exposed animals with 20mg/kg of vinpocetine restored both their locomotor activity and cAMP levels to control levels. CONCLUSIONS: These data lend support to the idea that cAMP signaling system contribute to the hyperactivity induced by developmental alcohol exposure and provide evidence for the potential therapeutic use of vinpocetine in FASD.
Assuntos
Consumo de Bebidas Alcoólicas/patologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtornos do Espectro Alcoólico Fetal/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Alcaloides de Vinca/farmacologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Animais , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Depressores do Sistema Nervoso Central/efeitos adversos , Depressores do Sistema Nervoso Central/sangue , Depressores do Sistema Nervoso Central/toxicidade , AMP Cíclico/análise , Modelos Animais de Doenças , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos , Etanol/efeitos adversos , Etanol/sangue , Etanol/toxicidade , Feminino , Humanos , Masculino , Camundongos , Inibidores de Fosfodiesterase/administração & dosagem , Inibidores de Fosfodiesterase/efeitos adversos , Inibidores de Fosfodiesterase/uso terapêutico , Gravidez , Complicações na Gravidez/induzido quimicamente , Método Simples-Cego , Taxa de Sobrevida , Alcaloides de Vinca/administração & dosagem , Alcaloides de Vinca/efeitos adversos , Alcaloides de Vinca/uso terapêutico , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Binge drinking (BD), which is characterized by sporadic consumption of large quantities of alcohol in short periods, is prevalent among university students. Animal studies have shown that BD is associated with damage to the hippocampus, a region of the brain that plays a key role in learning and memory. The temporal cortex undergoes structural and functional changes during adolescence. The aim of the present study was to examine the association between BD and declarative memory in male and female university students. METHODS: The participants were 122 students (between 18 and 20 years of age): 62 BD (30 women) and 60 non-BD (29 women). The neuropsychological assessment included the Rey Auditory Verbal Learning Test (RAVLT) and Weschler Memory Scale-3rd ed. (WMS-III) Logical Memory subtest, to evaluate verbal declarative memory, and the WMS-III Family Pictures subtest, to measure visual declarative memory. RESULTS: The BD students remembered fewer words in the interference list and displayed greater proactive interference in the RAVLT; they performed worse in the Logical Memory subtest, both on immediate and delayed recall. There were no differences between the groups in performance of the Family Pictures subtest. No significant interactions were observed between BD and sex. CONCLUSIONS: Binge drinking is associated with poorer verbal declarative memory, regardless of sex. The findings are consistent with the vulnerability of the adolescent hippocampus to the neurotoxic effects of alcohol. Longitudinal studies will help determine the nature of this relationship, the neurodevelopmental trajectories for each sex, and the repercussions on academic performance.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Depressores do Sistema Nervoso Central/intoxicação , Etanol/intoxicação , Memória/efeitos dos fármacos , Estudantes/psicologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/patologia , Consumo de Bebidas Alcoólicas/tendências , Chile/epidemiologia , Chile/etnologia , Feminino , Humanos , Masculino , Psicometria , Caracteres Sexuais , Universidades , Aprendizagem Verbal/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: Chronic ethanol intake leads to reproductive damage including reactive oxygen species formation, which accelerates the oxidative process. Melatonin is known to regulate the reproductive cycle, food/liquid intake, and it may also act as a potent antioxidant indoleamine. The aim of this study was to verify the effects of alcoholism and melatonin treatment on overall feed efficiency and to analyze its protective role against the oxidative stress in the ovarian tissue of UChB rats (submitted to 10% [v/v] voluntary ethanol consumption). METHODS: Forty adult female rats (n = 10/group) were finally selected for this study: UChB Co: drinking water only; and UChB EtOH: drinking ethanol at 2 to 6 ml/100 g/d + water, both receiving 0.9% NaCl + 95% ethanol 0.04 ml as vehicle. Concomitantly, UChB Co + M and UChB EtOH + M groups were infused with vehicle + melatonin (100 µg/100 g body weight/d) intraperitoneally over 60 days. All animals were euthanized by decapitation during the morning estrus (4 am). RESULTS: Body weight gain was reduced with ethanol plus melatonin after 40 days of treatment. In both melatonin-treated groups, it was observed a reduction in food-derived calories and liquid intake toward the end of treatment. The amount of consumed ethanol dropped during the treatment. Estrous cycle was longer in rats that received both ethanol and melatonin, with prolonged diestrus. Following to oxidative status, lipid hydroperoxide levels were higher in the ovaries of ethanol-preferring rats and decreased after melatonin treatment. Additionally, antioxidant activities of superoxide dismutase, glutathione peroxidase activity, and glutathione reductase activity were increased in melatonin-treated groups. CONCLUSIONS: We suggest that melatonin is able to affect feed efficiency and, conversely, it protects the ovaries against the oxidative stress arising from ethanol consumption.
Assuntos
Antioxidantes/farmacologia , Melatonina/farmacologia , Ovário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Consumo de Bebidas Alcoólicas/patologia , Animais , Antioxidantes/administração & dosagem , Peso Corporal/efeitos dos fármacos , Depressores do Sistema Nervoso Central/farmacologia , Depressores do Sistema Nervoso Central/toxicidade , Ciclo Estral/efeitos dos fármacos , Etanol/farmacologia , Etanol/toxicidade , Comportamento Alimentar/efeitos dos fármacos , Feminino , Índice Glicêmico/efeitos dos fármacos , Injeções Intraperitoneais , Melatonina/administração & dosagem , Ovário/lesões , Substâncias Protetoras/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fatores de TempoRESUMO
OBJECTIVE: To assess cytogenetic abnormalities through quantification of micronuclei, broken eggs, and karyorrhexis, in cells from normal oral mucosa of individuals exposed to carcinogens (alcohol and tobacco) and adjacent to leukoplakias and squamous cell carcinomas. STUDY DESIGN: The sample was composed of 40 subjects aged > 30 years, divided into four groups: control, alcohol/tobacco, leukoplakia, and squamous cell carcinoma. For control and alcohol/tobacco groups, cells were collected from lower lip, tongue border, and floor of the mouth. For leukoplakia and squamous cell carcinoma groups, mucosa contralateral and adjacent to the lesions were analyzed. Cytologic smears were stained with the Feulgen reaction. A blind observer analyzed 1,000 cells per slide to quantify micronuclei, broken eggs, and karyorrhexis. RESULTS: The leukoplakia group showed an increased number of micronuclei compared to controls (p = 0.0016) and the alcohol/tobacco group (p = 0.0048) and also increased broken eggs compared to the alcohol/tobacco group (p = 0.0172). Similarly, the carcinoma group presented more micronuclei compared to controls (p = 0.0462) and more broken eggs compared to the alcohol/tobacco group (p = 0.0104). CONCLUSION: The assessment of cytogenetic abnormalities micronuclei and broken eggs may be useful for monitoring individuals exposed to risk factors for developing oral cancer.
Assuntos
Carcinoma de Células Escamosas/genética , Aberrações Cromossômicas , Leucoplasia Oral/genética , Mucosa Bucal/fisiologia , Neoplasias Bucais/genética , Adulto , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/patologia , Carcinoma de Células Escamosas/patologia , Núcleo Celular/patologia , Humanos , Leucoplasia Oral/patologia , Masculino , Micronúcleos com Defeito Cromossômico , Testes para Micronúcleos , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Fumar/genética , Fumar/patologiaRESUMO
El Cáncer de Esófago ocupa el noveno lugar entre las neoplasias malignas a nivel mundial y está asociado al hábito tabáquico y alcohólico. En el Hospital Vargas de Caracas ocupa el lugar número 11 entre las primeras 15 (2.5%) causas de egresos por cáncer al año. Determinar el consumo de tabaco y alcohol en pacientes ingresados por Cáncer de esófago en el Hospital Vargas de Caracas durante el período 2004 - 2009. Se realizó estudio retrospectivo y descriptivo, luego de la revisión de historias de 24 pacientes ingresados por cáncer de esófago con diagnóstico de cáncer de esófago. Se utilizaron medidas de tendencia central para interpretación de resultados. 21(87.5%) de los pacientes fueron masculinos y 3(12.5%), femeninos. La edad promedio fue de 61 años. El 83.3%(20) refirieron hábito tabáquico de más de 24 paquetes/año y hábito alcohólico mayor a 120 gr/día. Histológicamente 87.5% (21) correspondió a Carcinoma Epidermoide localizados en 1/3 medio de esófago en 58.3% (14). Adenocarcinoma fue diagnosticado en 3 pacientes (12.5%) El hallazgo histopatológico más frecuente fue el carcinoma epidermoide en el 87.5% de las historias revisadas. El 83% de los pacientes tenían una asociación importante al hábito tabáquico y alcohólico, por lo que recomendamos implementación de Programa conjunto de promoción y prevención en salud entre la Sociedad Venezolana de Gastroenterología y la Sociedad Anticancerosa de Venezuela, de lucha contra los factores de riesgo de esta enfermedad...
Esophageal cancer ranks ninth among malignancies worldwide and is associated with smoking and alcoholism. In Hospital Vargas de Caracas is ranked number 11 among the top 15 (2.5%) causes of cancer discharges per year. To determine the consumption of tobacco and alcohol in patients admitted due to esophageal cancer in Hospital Vargas de Caracas during 2004-2009. A retrospective descriptive study was performed after reviewing the charts of 24 patients admitted with esophageal cancer. We used central tendency measures for interpretation of results. 21 (87.5%) patients were male and three (12.5%) female. The average age was 61 years-old. 83.3% (20) reported smoking over 24 pack/years and become an alcoholic greater than 120 g/day. Histologically, 87.5% (21) corresponded to epidermoid carcinoma located in 1/3 of the esophagus in 58.3% (14). Adenocarcinoma was diagnosed in 3 patients (12.5%). The most common histopathological fi nding was squamous cell carcinoma in 87.5% of the charts reviewed. 83% of patients had a signifi cant association with smoking and alcoholism, thats why, we recommend the implementation of a joint program in health promotion and disease prevention among the Venezuelan Society of Gastroenterology and Cancer Society of Venezuela, to fight against the risk factors of this disease...
Assuntos
Humanos , Masculino , Feminino , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/patologia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/diagnóstico , Uso de Tabaco/efeitos adversos , Uso de Tabaco/patologia , Gastroenterologia , OncologiaRESUMO
The effects of ethanol alone on the oral mucosa are still poorly understood, especially because there are few non-smoking chronic consumers of alcoholic beverages. The aim of this study was to evaluate the frequency of micronucleus, abnormal nucleus/cytoplasm ratio, pyknosis, karyorrhexis and karyolysis in exfoliated cells from the buccal mucosa and from the lateral border of the tongue in 36 non-smoker alcoholics (ethanol group) and 18 non-smokers and non-drinkers (control group). The Papanicolaou method was used. Since alcoholics generally have hepatobiliary involvement, the association between serum gamma-glutamyl transpeptidase (GGT) and some of the analyzed oral mucosa alterations was also investigated. The ethanol group showed a significant increase in the frequency of all alterations analyzed in the tongue cells when compared with the control group (p < 0.01; Mann-Whitney). However, the presence of these changes in buccal mucosa cells was not statistically significant (p > 0.05; Mann-Whitney). In the ethanol group, the correlation between serum GGT and the frequency of micronucleus and abnormal nucleus/cytoplasm ratio in oral mucosa cells was not significant (p > 0.05; Spearman). In conclusion, chronic exposure to ethanol may be associated with carcinogenic cytologic changes in the oral mucosa, even in the absence of tobacco smoking. These alterations were not correlated with hepatobiliary injury.
Assuntos
Consumo de Bebidas Alcoólicas/patologia , Alcoolismo/patologia , Etanol/efeitos adversos , Mucosa Bucal/patologia , Neoplasias Bucais/etiologia , gama-Glutamiltransferase/sangue , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Núcleo Celular/patologia , Humanos , Hepatopatias Alcoólicas , Masculino , Testes para Micronúcleos , Mucosa Bucal/efeitos dos fármacos , Fatores de Risco , Fumar/efeitos adversos , Estatísticas não ParamétricasRESUMO
Os efeitos do etanol isoladamente sobre a mucosa bucal permanecem pouco esclarecidos, sobretudo devido ao baixo número de não-fumantes consumidores crônicos de bebidas alcoólicas. O objetivo deste estudo foi avaliar as freqüências de micronúcleo, relação núcleo/citoplasma anormal, picnose, cariorrexe e cariólise em células esfoliadas da mucosa jugal e do bordo lateral da língua de 36 alcoólatras não-fumantes (grupo etanol) e 18 abstêmios de álcool e fumo (grupo controle). O método de Papanicolaou foi utilizado. Uma vez que indivíduos alcoólatras geralmente apresentam comprometimento hepatobiliar, a associação entre gama-glutamil transpeptidase (GGT) sérica e algumas das alterações citológicas analisadas também foi investigada. O grupo etanol mostrou um aumento significativo nas freqüências de todas as alterações investigadas nas células da língua quando comparado ao grupo controle (p < 0,01; Mann-Whitney). No entanto, a presença de tais mudanças na mucosa jugal não foi estatisticamente significante (p > 0,05; Mann-Whitney). No grupo etanol, a correlação entre GGT sérica e as freqüências de micronúcleo e a relação núcleo/citoplasma anormal em células da mucosa bucal não foi significativa (p > 0,05; Spearman). Conclui-se que o consumo crônico de etanol pode estar associado a alterações citológicas carcinogênicas na mucosa bucal, mesmo na ausência de exposição ao fumo. Tais alterações não apresentaram correlação com o comprometimento hepatobiliar.