RESUMO
OBJECTIVES: Uncontrolled ingestion of alcohol has dramatic consequences on the entire organism that are also associated with the oxidation process induced by alcohol and elevate radical oxygen species. Resveratrol, a nonflavonoid phenol, shows well-documented antioxidant properties. We investigated the potential antioxidant ability of this natural compound in a mouse model of alcohol addiction. METHODS: We administered (per os) for 60 d 10 mg · kg-1 · d-1 of resveratrol in alcoholic adult male mice. Oxidative stress was evaluated by measuring serum-free oxygen radicals defense and free oxygen radical levels. Resveratrol metabolites were measured in the serum of mice that were administered with resveratrol. Finally, the effect of resveratrol on the alcohol-induced alteration of brain-derived neurotrophic factors (BDNF) in the liver was investigated. RESULTS: Prolonged consumption of resveratrol strongly counteracts serum radical oxygen species formation caused by chronic alcohol intake without effects on natural, free oxygen radical defense. The presence of resveratrol metabolites in the serum only of animals supplemented with resveratrol potentiates the evidence that the antioxidant effect observed is due to the ingestion of the natural compound. Moreover, resveratrol supplementation can counteract alcohol-induced BDNF elevation in the liver, which is the main target of organ alcohol-induced damage. CONCLUSIONS: The consumption of resveratrol through metabolite formation may play a protective role by decreasing free radical formation and modulating the BDNF involved in hepatic disruption induced by chronic alcohol consumption. Further investigation into the mechanism underlying the protective effect could reinforce the potential use of resveratrol as a dietary supplement to prevent damage associated with chronic alcohol abuse.
Assuntos
Alcoolismo , Estilbenos , Alcoolismo/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Etanol , Masculino , Camundongos , Estresse Oxidativo , Resveratrol/farmacologia , Estilbenos/farmacologiaRESUMO
BACKGROUND: The Italian National Institute of Health (Istituto Superiore di Sanità, ISS) considers health inequalities (HI) an important area of activity. As the scientific and technical body of the Ministry of Health and the National Health Service, ISS may play a key role to reduce HI. In order to enable ISS in addressing the new and crucial HI challenge, a Research Positioning Exercise was designed and implemented. METHODS: The Exercise included: (i) workshop to strengthen the institutional interest in the field of HI; (ii) review and analysis of ISS publications (years 2000-2017) to identify HI research topics; (iii) survey among ISS researchers regarding main research challenges to address HI in the coming years; and (iv) analysis of input on research challenges from HI international experts. RESULTS: The results of this Exercise suggest that the following points should be included in the future ISS agenda planning: (i) themes which ISS should continue working on (e.g. migrants/vulnerable groups); (ii) themes to be improved: (a) relationship between social determinants and mechanism of HI generation and (b) relationship between risk factors exposure and social determinants; and (iii) new themes to be addressed: (a) mechanisms underlying the resilience observed in Italy; (b) new socioeconomic indicators for HI monitoring; and (c) evidence-based policies aimed at reducing HI. CONCLUSION: Findings of this Exercise show that ISS researchers identified relevant areas, addressing inequalities in addressing the health. Because of ISS structural peculiarity that includes multidisciplinary expertise, the ISS could provide a significant contribution to HI research challenges and knowledge gaps.
Assuntos
Pesquisa Biomédica , Educação , Disparidades nos Níveis de Saúde , Proteínas de Arabidopsis , Pesquisa Biomédica/organização & administração , Órgãos Governamentais/organização & administração , Histona-Lisina N-Metiltransferase , Humanos , Itália/epidemiologia , Pesquisa , Fatores de Risco , Determinantes Sociais da Saúde , Populações VulneráveisRESUMO
Few animal studies focus on consequences of nicotine postnatal exposure, particularly through lactation. We have recently shown that forced nicotine drinking elevates maternal care, paradoxically provoking arousal and stress in pups. Present work aimed to evaluate the specific contribution of altered maternal cares, compared to the sequelae merely due to nicotine effects. Two groups were compared to water-drinking control dams: (i) free-choice dams (H2O+NIC group) drinking from two bottles, containing either nicotine or water; (ii) forced dams (NIC+NIC group) drinking from two bottles, both containing nicotine. We previously demonstrated that nicotine was indeed transferred to the lactating offspring. Regarding behavioural consequences at adolescence, both H2O+NIC and NIC+NIC rats were slower than controls in discovering a novel over a familiar compartment, whilst only NIC+NIC rats exhibited reduced risk-related avoidance and assessment behaviour. Brain analyses at adulthood suggest that, in prefrontal cortex, nicotine per se reduced serotonin, while the maternal overcare reduced CHRN-B2 gene-expression. As a whole, unescapable nicotine-enhanced maternal care could have an impact on the offspring arousal by acting on prefrontal CHRN-B2 gene-expression. When present results are translated to consequences of non-voluntary exposure in humans, we propose that children receiving altered attentions by a smoking caregiver might undergo a neuro-behavioural development biased towards emotional shyness.
Assuntos
Lactação , Exposição Materna/efeitos adversos , Nicotina/efeitos adversos , Agonistas Nicotínicos/efeitos adversos , Receptores Nicotínicos/metabolismo , Assunção de Riscos , Animais , Comportamento de Escolha , Comportamento Exploratório/efeitos dos fármacos , Comportamento Alimentar , Feminino , Expressão Gênica/efeitos dos fármacos , Masculino , Comportamento Materno/efeitos dos fármacos , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/crescimento & desenvolvimento , Distribuição Aleatória , Ratos Wistar , Serotonina/metabolismoRESUMO
This study investigates the transfer of nicotine from lactating dams to their offspring through breast milk, in the frame of a research focused to ascertain toxicological and neuro-behavioural effects on pups as consequence of either unavoidable ("yoked & forced") or voluntary ("freely-chosen") maternal nicotine exposure. To this aim, plasmatic concentrations of nicotine and cotinine were determined by LC-MS/MS in Wistar rat pups whose mothers were orally administered with nicotine during lactation. Mothers were divided into a voluntary drinking group, an unavoidable consumption group, and controls. The limits of detection and quantification of the LC-MS/MS method were 0.20 and 0.65 ng/mL, respectively. Within-laboratory reproducibility (CV%) was <12%, with recovery of 86.2-118.8%. Results showed the presence of nicotine in 67% of samples from freely-chosen consumption group (1.30 ± 0.31 ng/mL) and in 60% of samples from yoked-consumption group (1.19 ± 0.62 ng/mL); cotinine was found in all the samples from freely-chosen (1.92 ± 0.77 ng/mL) and yoked-consumption groups (1.43 ± 0.30 ng/mL). Data provide an evidence-based support to maternal/offspring nicotine transfer as function of different ways of oral exposure.
Assuntos
Comportamento Animal/efeitos dos fármacos , Lactação , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Animais , Aleitamento Materno , Cotinina/sangue , Feminino , Masculino , Leite/química , Nicotina/farmacocinética , Agonistas Nicotínicos/farmacocinética , Ratos , Ratos WistarRESUMO
Adverse effects of nicotine during pregnancy have been greatly studied, while nowadays few works are focused on consequences of maternal tobacco smoking after birth. The present study investigated the behavioral and early neurochemical effects of nicotine treatment during first weeks of post-natal life in rats. We used "free choice" treatment (H2O+NIC dams could drink from two bottles, containing 10mg/L nicotine hydrogen tartrate salt, or water) versus "forced choice" (NIC+NIC mothers could drink from two bottles both containing nicotine hydrogen tartrate salt, range from 0.75mg/L to 4.09mg/L). We found that only "forced nicotine" had impact on maternal behavior, causing increased high-quality maternal care. This immediately impacted on neuro-chemical development, affecting NE levels (only males) in pup's striatum and prefrontal cortex (pFC) at PND 12. After weaning, animals were reared in normal conditions (two brother rats) or in Social Isolation. After two weeks, they were tested with Social Interaction Test (isolated rats met non-isolated opponents, siblings vs. non-siblings). As expected, isolated rats displayed an aggressive form of soliciting behavior: when facing an isolated unknown partner, the non-isolated rat tried to escape. Interestingly, if their dams were exposed to forced nicotine, both rats sooner behaved very affiliative (possibly empathic) between non-sibling partners. As expected, being exposed to post-natal nicotine could alter neuro-chemical development, but with important interactions between both maternal care and adolescent social behavior.
Assuntos
Comportamento Animal/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Exposição Materna/efeitos adversos , Nicotina/farmacologia , Isolamento Social , Animais , Animais Recém-Nascidos , Feminino , Lactação/efeitos dos fármacos , Masculino , Comportamento Materno/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , DesmameRESUMO
Ethyl glucuronide (EtG) is an ethanol metabolite and EtG is used as a biomarker of alcohol drinking. EtG can be detected in the blood and in several biological matrices including urine, hair and nails. Alcohol consumption during pregnancy is a strong risk factor for fetus health so in the recent years different strategies to reveal alcohol use have been planning including the use of screening questionnaires as the AUDIT-C, T-ACE and TWEAK. The present study aims to investigate in pregnant women the specificity and predictive value of the AUDIT-C, T-ACE and TWEAK plus a food diary in use in Sapienza University Hospital compared with the results of urine EtG measurement. Seventy pregnant women were enrolled and examined. Urine samples were provided by pregnant women immediately after the interviews. EtG determinations were performed by Enzyme Immunoassay with a cut-off established at 100ng/mL. Data show that 34.28% of the enrolled pregnant women overcame the EtG cut off. No direct correlation was found between EtG data and the alcohol screening interviews showing lower levels of alcohol consumption, although T-ACE revealed the same at risk percentage. However, a significant concordance was observed with food diary data and T-ACE only in patients with higher EtG urinary concentration. This study provides clinical evidence that the diagnosis of maternal alcohol consumption during pregnancy only based on indirect methods, such as questionnaires and food diary, may significantly underestimate alcohol use.
Assuntos
Consumo de Bebidas Alcoólicas/urina , Etanol/metabolismo , Glucuronatos/urina , Exposição Materna , Gravidez/urina , Detecção do Abuso de Substâncias/métodos , Adulto , Biomarcadores/urina , Etanol/efeitos adversos , Feminino , Humanos , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Alcohol addiction elicits oxidative imbalance and it is well known that polyphenols possess antioxidant properties. We investigated whether or not polyphenols could confer a protective potential against alcohol-induced oxidative stress. METHODS: We administered (per os) for two months 20 mg/kg of olive polyphenols containing mostly hydroxytyrosol in alcoholic adult male mice. Hydroxytyrosol metabolites as hydroxytyrosol sulfate 1 and hydroxytyrosol sulfate 2 were found in the serum of mice administered with polyphenols with the highest amount in animals treated with both polyphenols and alcohol. Oxidative stress was evaluated by FORT (free oxygen radical test) and FORD (free oxygen radical defense) tests. RESULTS: Alcoholic mice showed a worse oxidative status than nonalcoholic mice (higher FORT and lower FORD) but polyphenol supplementation partially counteracted the alcohol pro-oxidant effects, as evidenced by FORT. CONCLUSIONS: A better understanding of the antioxidant protection provided by polyphenols might be of primary interest for drug discovery and dietary-based prevention of the damage associated with chronic alcohol abuse.
Assuntos
Alcoolismo/metabolismo , Antioxidantes/farmacologia , Etanol/efeitos adversos , Olea/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Animais , Comportamento Aditivo , Doença Crônica , Suplementos Nutricionais , Radicais Livres , Masculino , Camundongos , OxirreduçãoRESUMO
A liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of nicotine and seven minor tobacco alkaloids in both refill liquids for electronic cigarettes and their generated aerosol was developed and validated. The limit of detection and limit of quantification values were 0.3-20.0 and 1.0-31.8 ng/mL, respectively. Within-laboratory reproducibility was 8.2-14.2% at limit of quantification values and 4.8-12.7% at other concentration levels. Interday recovery was 75.8-116.4%. The method was applied to evaluate the compliance of commercial liquids (n = 95) with their labels and to assess levels of minor alkaloids. Levels of nicotine and its corresponding compounds were also evaluated in generated aerosol. About 47% of samples showed differences above ±10 % of the stated nicotine concentration. About 78% of the "zero nicotine" liquids showed traces in the range of 1.3 ± 0.1-254.0 ± 14.6 µg/mL. Nicotine-N'-oxides, myosmine, and anatabine were the most common minor alkaloids in liquids containing nicotine. Nicotine and N'-oxides were detected in all air samples when aerosol was generated from liquids containing nicotine. Nicotine average emissions from electronic cigarette (2.7 ± 0.9 µg/m3 ) were significantly lower (p < 0.01, t-test) with respect to conventional cigarette (30.2 ± 1.5 µg/m3 ).
Assuntos
Alcaloides/análise , Cromatografia Líquida , Sistemas Eletrônicos de Liberação de Nicotina , Nicotina/análise , Espectrometria de Massas em Tandem , Aerossóis/análise , Reprodutibilidade dos Testes , Nicotiana/químicaRESUMO
Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Pai , Fator de Crescimento Neural/efeitos dos fármacos , Alcoolismo/fisiopatologia , Animais , Western Blotting , Encéfalo/efeitos dos fármacos , Cromatografia Gasosa , Modelos Animais de Doenças , Masculino , Camundongos , Recompensa , Sacarose/administração & dosagemRESUMO
AIMS: The role of the serotonin transporter gene (SLC6A4) in alcohol dependence (AD) is still unclear. In this paper, we have evaluated the association of the SLC6A4 gene polymorphisms 5-HTTLPR and rs25531 in AD and assessed the polymorphic patterns both in alcoholics and in healthy people of an Italian population. METHODS: Genotyping of the 5-HTTLPR (L/S) and rs25531 (A/G) polymorphisms of the SLC6A4 gene was performed on 403 alcoholics outpatients and 427 blood donors. RESULTS: Comparing AD and control populations and taking into account statistical correction for multiple testing, we found no statistically significant differences for 5-HTTLPR (L/S) and rs25531 polymorphisms in terms of either genotypes or alleles frequencies. By univariate ANOVA, a statistically significant difference was found in the onset of AD: the mean age of onset resulted to be of 25.4 years in males in respect to 28.1 in females. In particular in males, the early AD onset was different, in a statistically significant manner, depending on the presence of at least one S or Lg allele (24.6 years) in respect to La homozygotes (27.5 years) (P = 0.03). CONCLUSIONS: These findings suggest that genetic factors contribute, together with gender and age, to the onset differences in alcohol-dependent phenotypes.
Assuntos
Alcoolismo/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , População Branca/genética , Adolescente , Adulto , Idade de Início , Idoso , Alcoolismo/epidemiologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Adulto JovemRESUMO
INTRODUCTION: To date, several concerns have been raised on the purity of ingredients employed in the manufacturing processes of refill fluids and cartridges, the device functionality, and the quality control of electronic cigarettes. This article reviews analytical methods so far described for the analysis of liquids to detect their chemical components and to investigate the presence of toxicants and carcinogens that can potentially occur as impurities of ingredients or as a consequence of their degradation. RESULTS AND DISCUSSION: Based on the scientific literature, high-performance liquid chromatography with diode-array detection (HPLC/DAD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) are most appropriate for determining nicotine and related compounds in fluids and cartridges, whereas LC-MS/MS has been successfully used to determine nitrosamines. Content analyses of glycols have been performed using gas chromatography equipped with flame ionization detector or gas chromatography/mass spectrometry (GC/MS), whereas carbonyl and other volatile organic compounds determinations have been performed by HPLC/DAD and GC/MS, respectively. Content analyses of heavy metals have been performed by inductively coupled plasma optical emission spectroscopy or inductively coupled plasma mass spectrometry. Since new potentially toxic substances may be created during heating, it is also necessary to investigate the chemical composition of generated aerosol. In this case, similar methods applied for tobacco smoke can be adopted. CONCLUSIONS: A broad range of analytical techniques are available for the detection of constituents and toxicants in e-liquids and cartridges. Analyses of liquids have been performed with pharmacopeia procedures and methods (International Organization for Standardization, Environmental Protection Agency, and American Public Health Association) developed for other matrices but applicable to e-liquids. Because new potentially harmful substances may be produced during heating process, analyses of aerosol are needed to correlate its composition to the chemical components of liquids.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/normas , Cromatografia Gasosa-Espectrometria de Massas/métodos , Nicotina/análise , Nicotina/química , Espectrometria de Massas em Tandem/métodos , Carcinógenos/análise , Carcinógenos/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Cromatografia Líquida/métodos , Cromatografia Líquida/normas , Cromatografia Gasosa-Espectrometria de Massas/normas , Nitrosaminas/análise , Nitrosaminas/química , Fumaça/análise , Espectrometria de Massas em Tandem/normas , Nicotiana/químicaRESUMO
OBJECTIVES: Fetal Alcohol Spectrum Disorders (FASD) due to prenatal ethanol consumption may induce long-lasting changes to the newborns affecting also the endocrine system and the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) signaling. Thus the aim of this study was to investigate in the thyroid, testis and adrenal glands of a FASD mouse model the long-lasting effects of ethanol exposure during pregnancy and lactation on NGF and BDNF and their main receptors, TrkA and TrkB, including their phosphorylated patterns. METHODS: We used aged male CD-1 mice early exposed to ethanol solution or red wine at same ethanol concentration (11% vol). RESULTS: We found elevations in NGF and BDNF in the thyroid of aged mice exposed to ethanol solution only but not in the red wine group. In the testis NGF resulted to be increased only in the ethanol solution group. In the adrenal glands data showed an elevation in NGF in both the ethanol solution group and red wine. No changes in TrkA, TrkB, phospho-TrkA and phospho-TrkB were revealed in all tissues examined. CONCLUSIONS: Early administration of ethanol may induce long-lasting changes in the mouse thyroid, testis and adrenal glands at NGF and BDNF levels.
Assuntos
Glândulas Suprarrenais/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtornos do Espectro Alcoólico Fetal/metabolismo , Fator de Crescimento Neural/metabolismo , Testículo/metabolismo , Glândula Tireoide/metabolismo , Animais , Feminino , Masculino , Camundongos , GravidezRESUMO
INTRODUCTION: Long term alcohol abuse is associated with deficiencies in essential nutrients and minerals that can cause a variety of medical consequences including accumulation of toxic metals. AIM: The aim of this research is to get evidence-based data to evaluate alcohol damage and to optimize treatment. Thiamine and thiamine diphosphate (T/TDP), zinc (Zn), selenium (Se), lead (Pb) and oxidative stress in terms of reactive oxygen metabolites (ROMs) were examined in blood samples from 58 alcohol dependent patients (17 females and 41 males). RESULTS: T/TDP concentration in alcoholics resulted significantly lower than controls (p < 0.005) for both sexes. Serum Zn and Se did not significantly differ from reference values. Levels of blood Pb in alcoholics resulted significantly higher (p < 0.0001) than Italian reference values and were higher in females than in males. ROMs concentration was significantly higher than healthy population only in female abusers (p = 0.005). CONCLUSION: Alcoholics show a significant increase in blood oxidative stress and Pb and decrease in thiamine. Impairment occurs mainly in female abusers confirming a gender specific vulnerability.
Assuntos
Alcoólicos , Alcoolismo/sangue , Chumbo/sangue , Estresse Oxidativo/fisiologia , Selênio/sangue , Tiamina/sangue , Zinco/sangue , Adulto , Envelhecimento/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres SexuaisRESUMO
Prenatal ethanol exposure produces severe changes in brain, liver, and kidney through mechanisms involving growth factors. These molecules regulate survival, differentiation, maintenance, and connectivity of brain, liver, and kidney cells. Despite the abundant available data on the short and mid-lasting effects of ethanol intoxication, only few data show the long-lasting damage induced by early ethanol administration. The aim of this study was to investigate changes in nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) in brain areas, liver, and kidney of 18-mo-old male mice exposed perinatally to ethanol at 11% vol or to red wine at the same ethanol concentration. The authors found that ethanol per se elevated NGF, BDNF, HGF, and VEGF measured by ELISA in brain limbic system areas. In the liver, early exposure to ethanol solution and red wine depleted BDNF and VEGF concentrations. In the kidney, red wine exposure only decreased VEGF. In conclusion, the present study shows that, in aged mice, early administration of ethanol solution induced long-lasting damage at growth factor levels in frontal cortex, hippocampus, and liver but not in kidney. Otherwise, in mice exposed to red wine, significant changes were observed in the liver and kidney but not in the hippocampus and frontal cortex. The brain differences in ethanol-induced toxicity when ethanol is administered alone or in red wine may be related to compounds with antioxidant properties present in the red wine.
Assuntos
Encéfalo/metabolismo , Etanol/toxicidade , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fígado/metabolismo , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Vinho/toxicidade , Envelhecimento/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Etanol/farmacocinética , Feminino , Fator de Crescimento de Hepatócito/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Camundongos , Fator de Crescimento Neural/efeitos dos fármacos , Fator de Crescimento Neural/metabolismo , Especificidade de Órgãos , Gravidez , Distribuição Tecidual , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
This paper highlights gender peculiarities in the neuroscience of alcohol effects and draws attention to emerging problems due to simultaneous exposure to alcohol and environmental factors. All the available gender studies on alcohol show greater severity of alcohol-related damage, including brain damage, in females compared with males. The differences are due to physiological peculiarities that make women more vulnerable to the effects of alcohol. Today the trend to start consuming alcohol at a younger age, together with the growing number of women drinking excessively, is increasing the alcohol-related risks to women's health and justifying the need for better, gender-based studies of alcohol use and abuse. A further aspect to consider in this context is the risk of the occurrence of foetal alcohol spectrum disorders and foetal alcohol syndrome in the offspring of women who drink during pregnancy. Several lines of evidence indicate that prenatal ethanol exposure can influence cell proliferation and differentiation in the central nervous system, causing severe neurotoxicity and permanent birth defects.
Assuntos
Consumo de Bebidas Alcoólicas , Meio Ambiente , Neurociências/tendências , Saúde da Mulher , Fatores Etários , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/patologia , Alcoolismo/epidemiologia , Alcoolismo/etiologia , Alcoolismo/patologia , Encéfalo/patologia , Feminino , Transtornos do Espectro Alcoólico Fetal/etiologia , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-NatalRESUMO
Ethanol intake during pregnancy and lactation induces severe changes in brain and liver throughout mechanisms involving growth factors. These are signaling molecules regulating survival, differentiation, maintenance and connectivity of brain and liver cells. Ethanol is an element of red wine which contains also compounds with antioxidant properties. Aim of the study was to investigate differences in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) in brain areas and liver by ELISA of 1-month-old male mice exposed perinatally to ethanol at 11 vol.% or to red wine at same ethanol concentration. Ethanol was administered before and during pregnancy up to pups' weaning. Ethanol per se elevated HGF in liver and cortex, potentiated liver VEGF, reduced GDNF in the liver and decreased NGF content in hippocampus and cortex in the offspring. We did not find changes in HGF or NGF due to red wine exposure. However, we revealed elevation in VEGF levels in liver and reduced GDNF in the cortex of animals exposed to red wine but the VEGF liver increase was more marked in animals exposed to ethanol only compared to the red wine group. In conclusion the present findings in the mouse show differences in ethanol-induced toxicity when ethanol is administered alone or in red wine that may be related to compounds with antioxidant properties present in the red wine.
Assuntos
Etanol/efeitos adversos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/biossíntese , Fator de Crescimento de Hepatócito/biossíntese , Exposição Materna/efeitos adversos , Fator de Crescimento Neural/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Vinho , Animais , Animais Recém-Nascidos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/embriologia , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/embriologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Fígado/efeitos dos fármacos , Fígado/embriologia , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos , Gravidez , Vinho/efeitos adversosRESUMO
In Western countries alcohol misuse is the most frequent cause of thiamine (vitamin B1) deficiency (TD) and consequent neuro-impairment. Studies have demonstrated that between 30 and 80% of alcoholics are thiamine deficient, and this puts them at risk of developing the Wernicke-Korsakoff (WK) syndrome. The relative roles of alcohol and TD in causing brain damage remain controversial and it is important to try to determine the role played by each factor. Animal studies support an additive effect of alcohol exposure and TD, and indicate the potential for interaction between alcohol and TD in human alcohol-related brain damage. Early diagnosis of alcohol-related TD is therefore an important aspect of effective intervention and treatment. Alcohol biomarkers provide a direct and indirect way of estimating the amount of alcohol being consumed, the duration of ingestion and the harmful effects that long-term alcohol use has on body functions. Appropriate use of these markers is very helpful when considering a diagnosis of alcohol-related TD.
Assuntos
Alcoolismo/diagnóstico , Deficiência de Tiamina/diagnóstico , Deficiência de Tiamina/prevenção & controle , Alcoolismo/complicações , Alcoolismo/metabolismo , Biomarcadores , Humanos , Síndrome de Korsakoff/prevenção & controle , Testes de Função Hepática , Deficiência de Tiamina/etiologiaRESUMO
Ethanol exposure during pregnancy is one of the major causes of mental retardation in western countries by inducing fetal-alcohol-like-syndromes. Red wine is known to contain ethanol but also compounds with putative antioxidant properties. It has also been shown that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are severely affected by ethanol during prenatal and postnatal life. The aim of the current study was to investigate in male CD1 mice brain alterations in NGF and BDNF due to chronic early exposure to ethanol solution (11 vol%) or to red wine at the same alcohol concentration starting from 60 days before pregnancy up to pups weaning. Data revealed no differences between groups of dams in pregnancy duration, neither in pups delivery, pups mortality and sex ratio. Data also showed that adult animals exposed to only ethanol had disrupted levels of both NGF and BDNF in the hippocampus and other brain areas. This profile was associated with impaired ChAT immunopositivity in the septum and Nuclei Basalis and with altered cognition and emotional behavior. Quite interestingly mice exposed to red wine had no change in the behavior or in ChAT immunopositivity but a decrease in hippocampal BDNF and a mild NGF decrease in the cortex. Also NGF-induced neuritic outgrowth in PC-12 cells was still present when exposed to red wine but not when exposed to ethanol solution only. Data suggest differences in ethanol-induced neurotoxicity between red wine and ethanol solution only.
Assuntos
Peso Corporal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Etanol/toxicidade , Troca Materno-Fetal , Fator de Crescimento Neural/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Colina O-Acetiltransferase/análise , Cognição/efeitos dos fármacos , Emoções/efeitos dos fármacos , Etanol/administração & dosagem , Etanol/sangue , Feminino , Masculino , Camundongos , Gravidez , Vinho/efeitos adversosRESUMO
In Italy, little is known about the spectrum of adverse fetal effects related to maternal alcohol use during pregnancy. In this paper, we report on the phenotype of Italian children with fetal alcohol spectrum disorders (FASD). These data were gathered as part of a field study assessing the prevalence of FASD in children in an in-school study in a rural area near Rome. The purposes of this paper are: (1) to completely characterize the clinical phenotype of a large cohort of Italian children with FASD; (2) to correlate and contrast the phenotype of this population with that observed in other populations and reported in the medical literature; (3) to discuss the drinking habits of Italian women, before, during and after pregnancy; and (4) to suggest mechanisms for intervention and prevention of FASD based on data gathered from this study.