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1.
Chem Biol Interact ; 321: 109044, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32151596

RESUMO

Overconsumption of alcohol could lead to severe liver injury that connects with oxidative stress, apoptosis, and inflammatory response. Previously, we proved that p-coumaric acid prevents ethanol induced reproductive toxicity; however, p-coumaric acid (PCA) on ethanol mediated hepatotoxicity has not been examined yet. In our work, we sought to study the potential of PCA in contradiction of ethanol induced hepatoxicity which linking with MAPKs, apoptosis, oxidative stress, and Nrf2 signaling. Foremost, we found that PCA could protect ethanol induced both L-02 and HepG2 hepatic cells by inhibiting cytotoxicity, ROS production, mitochondrial depolarization, and nuclear fragmentation. Also, in vivo experiments showed that the ethanol increasing the lipid markers (TBARS, CD) and depletes the antioxidants thereby increased phosphorylation of JNK, ERK, and p38 in rat liver tissues. Interestingly, PCA treatments inhibit ethanol exposed lipid markers and depletion of antioxidants, which directs the inhibition of MAPKs activation in rat liver tissues. We also noticed that the PCA protected ethanol induced apoptosis and liver markers by inhibiting the expression of Bax, caspases; AST, ALT, ALS, and LDH in liver tissue. Overall, the ameliorative consequence of PCA on ethanol induced oxidative stress and apoptosis was achieved by suppressing the expression of CYP2E1 and overexpressing Nrf2 and its target protein HO-1 in rat liver tissue. As a result, PCA was marked to be an effective antioxidant with notable hepatoprotection by inhibiting MAPKs and apoptosis signaling via enhancing Nrf2 signaling.


Assuntos
Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/prevenção & controle , Propionatos/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Etanol/toxicidade , Células Hep G2 , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/lesões , Fígado/metabolismo , Hepatopatias Alcoólicas/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
2.
Chem Biol Interact ; 321: 108964, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32006539

RESUMO

Lupeol (1) was isolated from hexane branch extract of Maytenus salicifolia and the Lupeol stearate (2), Lupeol palmitate (3), Lupeol myristate (4), Lupeol laurate (5) and Lupeol caprylate (6) were obtained reacting 1 with an adequate carboxylic acid. Swiss mice were treated with vehicle, carbenoxolone or Lupeol esters before administration of ethanol/HCl or indomethacin. Additionally, the involvement of nitric oxide (NO), sulfhydryl compounds (NP-SH), α-2 adrenergic receptors (α2-AR) and prostaglandins (PGE) in antiulcer effects was investigated using appropriate inhibitors or antagonist. Oxidative and inflammatory parameters were measured after euthanasia and anti-secretory effects was evaluated in pylorus-ligated rats. Ethanol/HCl ulcerated the gastric mucosa by 64.45 ± 6.58 mm2, which the oral treatment with 1, 4 and 6 (10 mg/kg), and 3 and 5 (30 mg/kg) reduced the lesion area. Interestingly, 2 reduced the gastric ulcer by oral route in a potent and dose-dependent manner (ED50 = 0.40 mg/kg), which was accompanied by the increase in reduced glutathione levels and by the reduction of lipids peroxidation and myeloperoxidase and superoxide dismutase activities. Moreover, 2 (0.1 mg/kg) also prevented the ulcerogenesis by intraperitoneal route. The participation of NO, NP-SH, α2-AR and PGE in 2-mediated gastroprotection was confirmed. In indomethacin-induced ulcer, 2 (1 mg/kg, p.o) also reduced the ulcer area and increased the PGE2 levels. However, 2 did not alter the gastric acid secretion. Therefore, these findings indicate that the obtention of 2 potentiated the antiulcer activity of 1 and that this compound can elicit gastroprotective action due a diversified mode of action.


Assuntos
Antiulcerosos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/química , Modelos Animais de Doenças , Esterificação , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ácido Clorídrico/toxicidade , Indometacina/toxicidade , Camundongos , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico/metabolismo , Triterpenos Pentacíclicos/administração & dosagem , Triterpenos Pentacíclicos/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Relação Estrutura-Atividade
3.
Food Chem Toxicol ; 135: 110890, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31628963

RESUMO

Alcoholic liver disease is a major cause of morbidity and mortality worldwide. In this work, a food-grade recombinant Bacillus subtilis co-expressing both alcohol dehydrogenase from Saccharomyces cerevisiae (scADH) and aldehyde dehydrogenase from Issatchenkia terricola (istALDH) were successfully constructed via double-crossover homologous recombination. When cultured at 37 °C for 48 h, the activities of scADH and istALDH were 57.56 ±â€¯7.44 and 81.41 ±â€¯8.26 U/mL, respectively. In pH 4.0, the alcohol degradation rate of recombinant B. subtilis fmb8 was 33% and the ΔLog10 was 0.1, indicating that fmb8 could be used as whole-cell biocatalysts for biodegradation of alcohols under low pH conditions. Mice experiments indicated that recombinant B. subtilis significantly alleviate recombinant alcohol-induced increases of mouse liver index, blood alcohol content, and serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities. Furthermore, recombinant B. subtilis significantly reduced liver malondialdehyde levels and increased total antioxidant capacity and superoxide dismutase levels in mouse liver. Overall, our findings suggested that food-grade B. subtilis fmb8 co-expressing scADH and istALDH could be used as a potential probiotic for alcohol detoxification and alleviation of alcoholic liver injury.


Assuntos
Álcool Desidrogenase/genética , Aldeído Desidrogenase/genética , Bacillus subtilis/genética , Etanol/toxicidade , Inativação Metabólica , Álcool Desidrogenase/metabolismo , Aldeído Desidrogenase/metabolismo , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Etanol/sangue , Recombinação Homóloga , Camundongos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
4.
Toxicol Lett ; 321: 44-53, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31811911

RESUMO

This study was aimed to investigate the effect of prenatal ethanol exposure (PEE) on the susceptibility of offspring rats to glomerulosclerosis and to explore the mechanism. Pregnant Wistar rats were intragastrically administered ethanol (4g/kg·d) from gestational day (GD) 9 to GD 20, and the control group was given equal volume of normal saline. The offspring rats were all fed with high-fat diet after weaning, and were sacrificed at postnatal week 24 (PW24). The results revealed that the adult offspring kidneys in the male and female PEE groups exhibited higher glomerulosclerosis index and interstitial fibrosis index compared with the high-fat diet control groups, accompanied by elevated serum creatinine level. The protein expression of Nephrin and WT1, which were the marker genes of podocytes, was significantly decreased, whereas the protein expression of desmin and α-SMA, the marker genes of mesenchymal cells, was remarked enhanced in the male and female PEE groups. Compared with the high-fat diet control groups, the mRNA and protein expressions of renal angiotensin II receptor type 2 (AT2R) were decreased in the male PEE group, but increased in the female PEE group. PEE increased the mRNA and protein expressions of glucocorticoid (GC) activation system and inhibited the expression of insulin-like growth factor 1 (IGF1) signaling pathway in male offspring kidney; on the contrary, in female offspring kidney, PEE inhibited the mRNA and protein expression of glucocorticoid activation system and increased the expression of IGF1 signaling pathway. Taken together, PEE increased the susceptibility of the adult offspring to glomerulosclerosis, and the programming of renal AT2R or GC-IGF1 is respectively involved in the toxicity of PEE to the male or female offspring.


Assuntos
Dieta Hiperlipídica , Etanol/toxicidade , Glomerulonefrite/etiologia , Glomérulos Renais/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Transdução de Sinais/efeitos dos fármacos , Animais , Feminino , Fibrose , Regulação da Expressão Gênica , Idade Gestacional , Glomerulonefrite/genética , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Glucocorticoides/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Masculino , Gravidez , Ratos Wistar , Receptor Tipo 2 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/metabolismo , Transdução de Sinais/genética
5.
World J Microbiol Biotechnol ; 35(12): 189, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748890

RESUMO

Fossil fuels consumption impacts the greenhouse gas emissions. Biofuels are considered as alternative renewable energy sources to reduce the fossil fuels dependency. Bioethanol produced by recombinant microorganisms is a widely suggested alternative to increase the yield in fermentation processes. However, ethanol and acetate accumulation under the fermentation process had been described as important stressors for the metabolic capabilities of the microorganisms, stopping the fermentation process and affecting the ethanol yield. Ethanol tolerance is a determining factor in the improvement of fermentative properties of microorganisms; however understanding of ethanol tolerance is limited. The engineered Escherichia coli KO11 strain has been studied in detail and used as an ethanologenic bacteria model. The strain is capable of using glucose and xylose for an efficient ethanol yield. In the current work, the effect of the iron-sulfur cluster (ISC) over-expression in the KO11 strain, on its tolerance and ethanol yield, was evaluated. Fatty acids profiles of membrane phospholipids in the E. coli KO11 were modified under ethanol addition, but not due to the hscA mutation. The hscA mutation provoked a decrease in ethanol tolerance in the Kmp strain when was grown with 2% ethanol, in comparison to KO11 parent strain. Ethanol tolerance was improved in the mutant Kmp complemented with the recombinant isc gene cluster (pJC10 plasmid) from LD50 2.16% to LD50 3.8% ethanol. In batch fermentation on 1 L bioreactor using mineral medium with glucose (120 g/L), the KO11 strain showed ethanol production efficiencies of ~ 76.9%, while the hscA mutant (Kmp) ~ 75.4% and the transformed strain Kmp(pJC10) showed ~ 92.4% efficiency. Ethanol amount increase in the engineered Kmp(pJC10) strain was correlated with less organic acids (such as acetate and lactate) production in the fermentation medium (2.3 g/L), compared to that in the KO11 (17.05 g/L) and the Kmp (16.62 g/L). Alcohol dehydrogenase (ADH) activity was increased ~ 350% in the transformed Kmp(pJC10) strain, whereas in the Kmp mutant, the phosphoglycerate kinase (PGK), pyruvate kinase (PYK), and ADH activities were diminished, comparing to KO11. The results suggest that the isc system over-expression in the ethanologenic E. coli KO11 strain, increases ethanol yield mainly by improving ethanol tolerance and ADH activity, and by redirecting the metabolic flux from acetate synthesis to ethanol.


Assuntos
Ácidos/metabolismo , Tolerância a Medicamentos/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Etanol/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Família Multigênica/genética , Álcool Desidrogenase/genética , Técnicas de Cultura Celular por Lotes , Biocombustíveis , Reatores Biológicos , Escherichia coli/efeitos dos fármacos , Proteínas de Escherichia coli/genética , Etanol/toxicidade , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Fermentação , Engenharia Genética , Glucose/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas com Ferro-Enxofre/genética , Cinética , Redes e Vias Metabólicas/genética , Mutação , Xilose/metabolismo
6.
Life Sci ; 238: 116898, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610193

RESUMO

AIMS: Learning and memory impairment is a common symptom in the early stages of various types of dementia. It is likely to reduce the incidence of dementia with correct intervention. α-Asarone is the main bioactive substance isolated from Acorus tatarinowii Schott and has been proven to improve memory dysfunction; however, at present, the specific underlying mechanism is poorly understood. The aim of the present study was to investigate the effect of α-asarone on ethanol-impaired cognitive ability and explore the underlying mechanism in mice. MAIN METHODS: A mouse model of impaired learning and memory was created by ethanol (2.0 g/kg, i.g.). α-Asarone (7.5, 15 or 30 mg/kg, i.p.) was delivered 10 min prior to ethanol administration. The behavioral effect of α-asarone was evaluated using the novel object recognition test. Glutamate (Glu) and γ-aminobutyric acid (GABA) levels in the hippocampus were determined by ELISA, and the protein expression levels of hippocampal GluR2, NMDAR2B, SYNΙ, GLT-1 and CaMKⅡ were detected by western blotting. KEY FINDINGS: Pretreatment with α-asarone significantly improved the behavioral performance, regulated the imbalance of Glu and GABA in the hippocampus and the abnormal expression of related proteins. A possible underlying mechanism is regulation of the calcium signaling cascade to correct functioning of related proteins, and thus, maintain the level of Glu. SIGNIFICANCE: Our results show that the improvement in learning and memory elicited by α-asarone may providing a possible novel candidate for the prevention of learning and memory impairment in the early stages of dementia.


Assuntos
Anisóis/farmacologia , Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Fibrinolíticos/farmacologia , Hipocampo/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Animais , Modelos Animais de Doenças , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo
7.
Chem Commun (Camb) ; 55(86): 12912-12915, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31593207

RESUMO

Alcohol-induced liver injury has been a terrible threat to human health and life. The relationship between HClO and the process is unclear. Thus, a ratiometric two-photon fluorescent probe for HClO was deliberately constructed and revealed the generation of HClO in the alcohol-induced liver injury process for the first time.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Etanol/toxicidade , Células HeLa , Humanos , Ácido Hipocloroso/metabolismo , Camundongos , Microscopia de Fluorescência por Excitação Multifotônica , Imagem Óptica , Peixe-Zebra
8.
World J Gastroenterol ; 25(36): 5434-5450, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576091

RESUMO

BACKGROUND: High mobility group box-1 (HMGB1), recognized as a representative of damage-associated molecular patterns, is released during cell injury/death, triggering the inflammatory response and ultimately resulting in tissue damage. Dozens of studies have shown that HMGB1 is involved in certain diseases, but the details on how injured hepatocytes release HMGB1 need to be elicited. AIM: To reveal HMGB1 release mechanism in hepatocytes undergoing oxidative stress. METHODS: C57BL6/J male mice were fed a high-fat diet for 12 wk plus a single binge of ethanol to induce severe steatohepatitis. Hepatocytes treated with H2O2 were used to establish an in vitro model. Serum alanine aminotransferase, liver H2O2 content and catalase activity, lactate dehydrogenase and 8-hydroxy-2-deoxyguanosine content, nicotinamide adenine dinucleotide (NAD+) levels, and Sirtuin 1 (Sirt1) activity were detected by spectrophotometry. HMGB1 release was measured by enzyme linked immunosorbent assay. HMGB1 translocation was observed by immunohistochemistry/immunofluorescence or Western blot. Relative mRNA levels were assayed by qPCR and protein expression was detected by Western blot. Acetylated HMGB1 and poly(ADP-ribose)polymerase 1 (Parp1) were analyzed by Immunoprecipitation. RESULTS: When hepatocytes were damaged, HMGB1 translocated from the nucleus to the cytoplasm because of its hyperacetylation and was passively released outside both in vivo and in vitro. After treatment with Sirt1-siRNA or Sirt1 inhibitor (EX527), the hyperacetylated HMGB1 in hepatocytes increased, and Sirt1 activity inhibited by H2O2 could be reversed by Parp1 inhibitor (DIQ). Parp1 and Sirt1 are two NAD+-dependent enzymes which play major roles in the decision of a cell to live or die in the context of stress . We showed that NAD+ depletion attributed to Parp1 activation after DNA damage was caused by oxidative stress in hepatocytes and resulted in Sirt1 activity inhibition. On the contrary, Sirt1 suppressed Parp1 by negatively regulating its gene expression and deacetylation. CONCLUSION: The functional inhibition between Parp1 and Sirt1 leads to HMGB1 hyperacetylation, which leads to its translocation from the nucleus to the cytoplasm and finally outside the cell.


Assuntos
Fígado Gorduroso/patologia , Proteína HMGB1/metabolismo , Hepatócitos/patologia , Fígado/patologia , Sirtuína 1/metabolismo , Acetilação/efeitos dos fármacos , Animais , Carbazóis/farmacologia , Linhagem Celular , Núcleo Celular/metabolismo , Células Cultivadas , Citoplasma/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Etanol/toxicidade , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/etiologia , Hepatócitos/citologia , Humanos , Peróxido de Hidrogênio/toxicidade , Fígado/citologia , Fígado/efeitos dos fármacos , Testes de Função Hepática , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Poli(ADP-Ribose) Polimerase-1/metabolismo , Compostos de Quinolínio/farmacologia , RNA Interferente Pequeno/metabolismo , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/genética
9.
Adv Exp Med Biol ; 1164: 73-87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576541

RESUMO

The purpose of this review is to briefly summarize the roles of alcohol (ethanol) and related compounds in promoting cancer and inflammatory injury in many tissues. Long-term chronic heavy alcohol exposure is known to increase the chances of inflammation, oxidative DNA damage, and cancer development in many organs. The rates of alcohol-mediated organ damage and cancer risks are significantly elevated in the presence of co-morbidity factors such as poor nutrition, unhealthy diets, smoking, infection with bacteria or viruses, and exposure to pro-carcinogens. Chronic ingestion of alcohol and its metabolite acetaldehyde may initiate and/or promote the development of cancer in the liver, oral cavity, esophagus, stomach, gastrointestinal tract, pancreas, prostate, and female breast. In this chapter, we summarize the important roles of ethanol/acetaldehyde in promoting inflammatory injury and carcinogenesis in several tissues. We also review the updated roles of the ethanol-inducible cytochrome P450-2E1 (CYP2E1) and other cytochrome P450 isozymes in the metabolism of various potentially toxic substrates, and consequent toxicities, including carcinogenesis in different tissues. We also briefly describe the potential implications of endogenous ethanol produced by gut bacteria, as frequently observed in the experimental models and patients of nonalcoholic fatty liver disease, in promoting DNA mutation and cancer development in the liver and other tissues, including the gastrointestinal tract.


Assuntos
Transtornos Relacionados ao Uso de Álcool , Carcinogênese , Citocromo P-450 CYP2E1 , Sistema Enzimático do Citocromo P-450 , Etanol , Acetaldeído/toxicidade , Transtornos Relacionados ao Uso de Álcool/fisiopatologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Citocromo P-450 CYP2E1/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Etanol/toxicidade , Humanos , Isoformas de Proteínas
10.
Emergencias (Sant Vicenç dels Horts) ; 31(5): 341-345, oct. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-184124

RESUMO

Objetivo. Conocer la epidemiología de las consultas en urgencias por amnesia global transitoria (AGT), ya sea pura, asociada al consumo de tóxicos o en el contexto de una agresión sexual. Método. Estudio retrospectivo de enero a diciembre de 2018. Se revisaron las AGT atendidas en intoxicados (AGTtox), en víctimas de agresiones sexuales (AGTsex) y las amnesias puras (AGTpur), evaluando la presencia de tóxicos. Resultados. Se identificaron 287 AGT: 169 AGTsex (58,9%), 62 AGTpur (21,6%) y 56 AGTtox (19,5%). De ellas, 218 (76%) fueron mujeres y la edad osciló entre 16 y 90 años (60,6% menores de 30 años). Reconocieron consumo de alcohol 201 casos (72,8%), con etanolemia positiva en 105 (49,1%) (media de 0,74 g/l y máxima de 3,9 g/l). Admitieron consumo de cannabis 20 pacientes (7,1%), con analítica positiva en 39 casos (17,3%); cocaína 14 (4,9%), con analítica positiva en 28 (12,4%), y anfetaminas 5 (1,7%), con analítica positiva en 20 (8,8%). Presentaron sínto-mas de intoxicación 58 casos (20,1%). Cuatro pacientes ingresaron en coma. Se realizó una tomografía computariza-da (TC) craneal a 66 pacientes (23%), se hospitalizaron 7 y no hubo ningún fallecimiento. Conclusiones. La prevalencia de AGT es mayor si se incluyen los intoxicados y las agresiones sexuales, modificando la determinación de tóxicos la epidemiología de la AGT en urgencias


Objectives. To study the epidemiology of emergency department visits for transient global amnesia (TGA) by itself or associated with substance abuse or sexual assault. Methods. Retrospective study of cases treated from January to December 2018. Data for all patients with TGA were extracted, and cases were classified as associated with substance abuse (TGASUB), sexual assault (TGASEX), or neither (TGAONLY). Results. A total of 287 TGA cases were found: 169 (58.9%) were TGASEX, 62 (21.6%) TGAONLY, and 56 (19.5%) TGASUB. Two hundred eighteen (76%) were female and 69 (24%) were male. Ages ranged from 16 to 90 years; 174 (60.6%) were under the age of 30 years. Two hundred one patients (72.8%) reported consuming alcohol; and 105 (49.1%) were positive on testing (mean blood alcohol concentration, 0.74 g/L; maximum, 3.9 g/L. Twenty patients (7.1%) reported using cannabis, and 39 (17.3%) had positive test results; 14 reported using cocaine (4.9%) and 28 (12.4%) tested positive; 5 (1.7%) reported using amphetamines and 20 (8.8%) tested positive. Fifty-eight (20.1%) had symptoms of intoxication. Four were admitted in coma. A computed tomography scan was ordered for 66 patients (23%), 7 patients were hospitalized, and none died. Conclusions. The prevalence of TGA is higher if cases of substance abuse and sexual assault are counted. Toxicolgy testing changes the epidemiology of TGA in emergencies


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Amnésia Global Transitória/complicações , Amnésia Global Transitória/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Serviços Médicos de Emergência/métodos , Delitos Sexuais , Sintomas Toxicológicos/efeitos adversos , Estudos Retrospectivos , Coma/complicações , Coma/diagnóstico por imagem , Tomografia Computadorizada de Emissão , Etanol/toxicidade , Cocaína/toxicidade , Cannabis/toxicidade , Anfetaminas/toxicidade , Análise de Variância
11.
Nutrients ; 11(9)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546853

RESUMO

BACKGROUND: Dietary factors have significant effects on the brain, modulating mood, anxiety, motivation and cognition. To date, no attention has been paid to the consequences that the combination of ethanol (EtOH) and a high-fat diet (HFD) have on learning and mood disorders during adolescence. The aim of the present work was to evaluate the biochemical and behavioral consequences of ethanol binge drinking and an HFD consumption in adolescent mice. METHODS: Animals received either a standard diet or an HFD (ad libitum vs. binge pattern) in combination with ethanol binge drinking and were evaluated in anxiety and memory. The metabolic profile and gene expression of leptin receptors and clock genes were also evaluated. RESULTS: Excessive white adipose tissue and an increase in plasma insulin and leptin levels were mainly observed in ad libitum HFD + EtOH mice. An upregulation of the Lepr gene expression in the prefrontal cortex and the hippocampus was also observed in ad libitum HFD groups. EtOH-induced impairment on spatial memory retrieval was absent in mice exposed to an HFD, although the aversive memory deficits persisted. Mice bingeing on an HFD only showed an anxiolytic profile, without other alterations. We also observed a mismatch between Clock and Bmal1 expression in ad libitum HFD animals, which were mostly independent of EtOH bingeing. CONCLUSIONS: Our results confirm the bidirectional influence that occurs between the composition and intake pattern of a HFD and ethanol consumption during adolescence, even when the metabolic, behavioral and chronobiological effects of this interaction are dissociated.


Assuntos
Bulimia , Dieta Hiperlipídica , Etanol/toxicidade , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Adiposidade , Animais , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Hipocampo/metabolismo , Aprendizagem/fisiologia , Leptina/sangue , Masculino , Camundongos , Transtornos do Humor/etiologia , Transtornos do Humor/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Ganho de Peso
12.
Oxid Med Cell Longev ; 2019: 6029876, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396303

RESUMO

This study investigated the hepatoprotective effects of Morchella esculenta fruit body (ME) and the underlying mechanisms in mice with alcohol-induced acute liver injury. Systematic analysis revealed that ME contained 21 types of fatty acid, 17 types of amino acid, and 12 types of mineral. Subsequently, a mouse model of acute alcohol-induced liver injury was established by oral administration of alcohol for 14 days. Fourteen-day administration of ME prevented alcohol-induced increases in alanine aminotransferase and aspartate aminotransferase levels and reduced the activity of acetaldehyde dehydrogenase in blood serum and liver tissue. ME appears to regulate lipid metabolism by suppressing triglycerides, total cholesterol, and high-density lipoprotein in the liver. ME inhibited the production of inflammatory factors including chitinase-3-like protein 1 (YKL 40), interleukin-7 (IL-7), plasminogen activator inhibitor type 1 (PAI-1), and retinol-binding protein 4 (RBP4) in blood serum and/or liver tissue. ME treatment relieved the alcohol-induced imbalance in prooxidative and antioxidative signaling via nuclear factor-erythroid 2-related factor 2 (Nrf-2), as indicated by upregulation of superoxide dismutase-1, superoxide dismutase-2, catalase, heme oxygenase-1, and heme oxygenase-2 expression and downregulation of kelch-like ECH-associated protein 1 (Keap-1) in the liver. Moreover, ME reduced the levels of phosphorylated nuclear factor kappa-B kinase α/ß, inhibitor of nuclear factor kappa-B α and nuclear factor kappa-B p65 (NF-κB p65) in the liver. The hepatoprotective effects of ME against alcohol-induced acute liver injury were thus confirmed. The mechanism of action may be related to modulation of antioxidative and anti-inflammatory signaling pathways, partially via regulation of Nrf-2 and NF-κB signaling.


Assuntos
Ascomicetos/química , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Ascomicetos/metabolismo , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/veterinária , Etanol/toxicidade , Heme Oxigenase-1/metabolismo , Mediadores da Inflamação/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos
13.
Toxicol Lett ; 315: 87-95, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31425726

RESUMO

Prenatal alcohol exposure (PAE) is often associated with congenital heart defects, most commonly septal, valvular, and great vessel defects. However, there have been no known studies on whether PAE affects the resulting fibroblast population after development, and whether this has any consequences in the postnatal period. Our previous study focused on the effects of PAE on the postnatal fibroblast population, which translated into changes in cardiac extracellular matrix (ECM) composition and cardiac function in the neonatal heart. Moreover, our lab has previously demonstrated that alcohol-induced fibrosis is mediated by oxidative stress mechanisms in adult rat hearts following chronic alcohol exposure. Thus, we hypothesize that PAE alters cardiac ECM composition that persists into the postnatal period, leading to cardiac dysfunction, and these effects are prevented by antioxidant treatment. To investigate these effects, pregnant mice were intraperitoneally injected with 2.9 g EtOH/kg body weight on gestation days 6.75 and 7.25. Controls were injected with vehicle saline. Randomly selected dams in both groups were then treated with 100 mg/kg body weight of the antioxidant N-acetylcysteine (NAC) immediately after EtOH or vehicle administration. Left ventricular (LV) chamber dimension and function were assessed in sedated animals on neonatal day 5 using echocardiography. Ejection fraction decreased in the PAE group. NAC treatment prevented this depression of systolic function in PAE neonates. Hearts were analyzed for expression of fibroblast activation markers. Alpha smooth muscle actin (α-SMA) increased in PAE neonatal hearts, and this increase was prevented by NAC treatment. In PAE pups, collagen I decreased, but collagen III expression increased compared to saline animals; the overall collagen I/III ratio significantly decreased. When PAE mice were treated with NAC, collagen I/III ratio did not change. Overall, our data demonstrate that prenatal alcohol exposure produces changes in collagen subtype in neonatal cardiac ECM and a decline in systolic function, and these adverse effects were prevented by NAC treatment.


Assuntos
Acetilcisteína/farmacologia , Alcoolismo/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Vasos Coronários/química , Etanol/toxicidade , Fibroblastos/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Camundongos , Gravidez
14.
Oxid Med Cell Longev ; 2019: 3527809, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428222

RESUMO

Alcohol abuse has become common worldwide and has been recognized as a major cause of chronic alcoholic liver disease (ALD). ALD encompasses a complex process that includes a broad scope of hepatic lesions, ranging from steatosis to cirrhosis. In particular, reactive oxygen species (ROS) are mainly involved. Numerous studies have shown that p66shc plays a significant role in ALD. Protocatechuic acid (PCA), a dihydroxybenzoic acid that is naturally found in green tea, vegetables, and fruits, has efficient free radical scavenging effects. In this study, we aimed to assess the protective effect of PCA on ALD and to evaluate the microRNA- (miRNA-) p66shc-mediated reduction of ROS formation in ALD. Our results demonstrated that PCA treatment significantly decreased p66shc expression and downstream ROS formation in ALD. miR-219a-5p, which was identified by bioinformatics and experimental analysis, was enhanced by PCA and subsequently suppressed p66shc expression. Importantly, p66shc played an essential role in the protection of PCA-stimulated miR-219a-5p overexpression. Overall, these findings show that PCA-stimulated miR-219a-5p expression mitigates ALD by reducing p66shc-mediated ROS formation. This study may contribute to the development of therapeutic interventions for ALD.


Assuntos
Hidroxibenzoatos/farmacologia , Hepatopatias Alcoólicas/tratamento farmacológico , MicroRNAs/metabolismo , Substâncias Protetoras/uso terapêutico , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Regiões 3' não Traduzidas , Animais , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Etanol/toxicidade , Glutationa/metabolismo , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hidroxibenzoatos/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Masculino , Camundongos , MicroRNAs/química , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/química , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/genética , Superóxido Dismutase/metabolismo
15.
J Neuroinflammation ; 16(1): 136, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272469

RESUMO

BACKGROUND: Current evidence indicates that extracellular vesicles (EVs) participate in intercellular signaling, and in the regulation and amplification of neuroinflammation. We have previously shown that ethanol activates glial cells through Toll-like receptor 4 (TLR4) by triggering neuroinflammation. Here, we evaluate if ethanol and the TLR4 response change the release and inflammatory content of astrocyte-derived EVs, and whether these vesicles are capable of communicating with neurons by spreading neuroinflammation. METHODS: Cortical neurons and astrocytes in culture were used. EVs were isolated from the extracellular medium of the primary culture of the WT and TLR4-KO astrocytes treated with or without ethanol (40 mM) for 24 h. Flow cytometry, nanoparticle tracking analysis technology, combined with exosomal molecular markers (tetraspanins) along with electron microscopy, were used to characterize and quantify EVs. The content of EVs in inflammatory proteins, mRNA, and miRNAs was analyzed by Western blot and RT-PCR in both astrocyte-derived EVs and the neurons incubated or not with these EVs. Functional analyses of miRNAs were also performed. RESULTS: We show that ethanol increases the number of secreted nanovesicles and their content by raising the levels of both inflammatory-related proteins (TLR4, NFκB-p65, IL-1R, caspase-1, NLRP3) and by changing miRNAs (mir-146a, mir-182, and mir-200b) in the EVs from the WT-astrocytes compared with those from the untreated WT cells. No changes were observed in either the number of isolated EVs or their content between the untreated and ethanol-treated TLR4-KO astrocytes. We also show that astrocyte-derived EVs could be internalized by naïve cortical neurons to increase the neuronal levels of inflammatory protein (COX-2) and miRNAs (e.g., mir-146a) and to compromise their survival. The functional analysis of miRNAs revealed the regulatory role of the expressed miRNAs in some genes involved in several inflammatory pathways. CONCLUSIONS: These results suggest that astrocyte-derived EVs could act as cellular transmitters of inflammation signaling by spreading and amplifying the neuroinflammatory response induced by ethanol through TLR4 activation.


Assuntos
Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Etanol/toxicidade , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Células Cultivadas , Inflamação/induzido quimicamente , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/fisiologia , Receptor 4 Toll-Like/agonistas
16.
BMC Pharmacol Toxicol ; 20(1): 40, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277705

RESUMO

BACKGROUND: We aimed to determine the protective effects of thiamine pyrophosphate on ethanol induced optic neuropathy in an experimental model. METHODS: The rats were assigned into 4 groups, with 6 rats in each group as follows: healthy controls (HC group), only ethanol administered group (EtOH group), ethanol + thiamine pyrophosphate (20 mg/kg) administered group (TEt-20 group), and only thiamine pyrophosphate (20 mg/kg) (TPG group) administered group. To the rats in TEt-20 and TPG groups, 20 mg/kg thiamine pyrophosphate was administered via intraperitoneal route. To the rats in HC and EtOH groups, the same volume (0.5 ml) of distilled water as solvent was applied in the same manner. To the rats in TEt-20 and EtOH groups, one hour after application of thiamine pyrophosphate or distilled water, 32% ethanol with a dose of 5 g/kg was administered via oral gavage. This procedure was repeated once a day for 6 weeks. From the blood samples and tissues obtained from the rats, Malondialdehyde (MDA), reduced glutathione (GSH), interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) levels were studied. Histopathological evaluations were performed to the optic nerve tissue. RESULTS: Serum and tissue IL-1ß, TNF-α and MDA levels were the highest in EtOH group which were significantly lower in thiamine pyrophosphate administered group (TEt-20 group) (p: 0.001). Serum and tissue reduced GSH levels were the lowest in EtOH group which were also significantly higher in TEt-20 group (p:0.001). In histopathological evaluations, in EtOH group there was obvious destruction and edema with hemorrhage and dilated blood vessels which were not present in any other groups. CONCLUSIONS: There was an apparent destruction in ethanol administered group in histopathological analyses with an augmented level of oxidative stress markers and all those alterations were prevented with concomitant thiamine pyrophosphate administration. These protective effects of thiamine pyrophosphate are extremely important in chronic ethanol consumption. Clinical studies are warranted to define the exact role of thiamine pyrophosphate in prevention of ethanol induced optic neuropathy.


Assuntos
Etanol/toxicidade , Traumatismos do Nervo Óptico/induzido quimicamente , Traumatismos do Nervo Óptico/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Tiamina Pirofosfato/uso terapêutico , Animais , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/metabolismo , Nervo Óptico/patologia , Traumatismos do Nervo Óptico/metabolismo , Substâncias Protetoras/farmacologia , Ratos Wistar , Tiamina Pirofosfato/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
17.
Alcohol Alcohol ; 54(5): 465-471, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31361816

RESUMO

AIMS: In acute alcoholic liver injury, alcohol can directly or indirectly induce endoplasmic reticulum stress (ERS) to participate in liver injury, and it is found that the expression of serum exosomal miR-122 is significantly affected. Therefore, the present study investigated the effects of endoplasmic reticulum stress inhibition on the expression of serum exosomal miR-122 and acute liver injury. METHODS: The acute alcoholic liver injury models were established by the intragastric administration of ethanol (5 g/kg) in ICR mice. Intervention group received 4-phenylbutyric acid (PBA, endoplasmic reticulum stress inhibitor; 75 mg/kg and 150 mg/kg, intraperitoneal) 12 and 24 hours before intragastric administration. Mice treated with saline were used as controls. RESULTS: The ethanol treated mice exhibited significantly elevated hepatosomatic index (liver weight/body weight) and alanine aminotransferase (ALT), compared with those in the control group (P < 0.05). The ERS inhibitor 4-phenylbutyric acid protected against ethanol induced acute liver injury and hepatocyte necrosis, and PBA 150 mg/kg significantly attenuated ethanol induced hepatic ER stress-related proteins (GRP78, pIRE1α and pIF2α) (P < 0.05). Moreover, PBA 150 mg/kg markedly alleviated ethanol induced elevation of hepatic and serum exosomal miR-122 and pri-miR-122 (P < 0.05). CONCLUSIONS: These findings suggest that ER stress inhibitor PBA attenuated ethanol induced acute liver injury and serum exosomal miR-122, and provides a potential therapy strategy for acute alcoholic liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/sangue , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Etanol/toxicidade , Exossomos/metabolismo , MicroRNAs/sangue , Fenilbutiratos/uso terapêutico , Animais , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Estresse do Retículo Endoplasmático/fisiologia , Etanol/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fenilbutiratos/farmacologia , Distribuição Aleatória
18.
Biomed Res Int ; 2019: 2389485, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31346513

RESUMO

Acute alcohol exposure induces unconscious condition such as coma whose main physical manifestation is the loss of righting reflex (LORR). Xingnaojing Injection (XNJI), which came from Chinese classic formula An Gong Niu Huang Pill, is widely used for consciousness disorders in China, such as coma. Although XNJI efficiently shortened the duration of LORR induced by acute ethanol, it remains unknown how XNJI acts on ethanol-induced coma (EIC). We performed experiments to examine the effects of XNJI on orexin and adenosine (AD) signaling in the lateral hypothalamic area (LHA) in EIC rats. Results showed that XNJI reduced the duration of LORR, which implied that XNJI promotes recovery form coma. Microdialysis data indicated that acute ethanol significantly increased AD release in the LHA but had no effect on orexin A levels. The qPCR results displayed a significant reduction in the Orexin-1 receptors (OX1R) expression with a concomitant increase in the A1 receptor (A1R) and equilibrative nucleoside transporter type 1 (ENT1) expression in EIC rats. In contrast, XNJI reduced the extracellular AD levels but orexin A levels remained unaffected. XNJI also counteracted the downregulation of the OX1R expression and upregulation of A1R and ENT1 expression caused by EIC. As for ADK expression, XNJI but not ethanol, displayed an upregulation in the LHA in EIC rats. Based on these results, we suggest that XNJI promotes arousal by inhibiting adenosine neurotransmission via reducing AD level and the expression of A1R and ENT1.


Assuntos
Proteínas de Transporte/genética , Coma/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Receptor A1 de Adenosina/genética , Adenosina/genética , Adenosina/metabolismo , Animais , Coma/induzido quimicamente , Coma/genética , Coma/patologia , Etanol/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Região Hipotalâmica Lateral/efeitos dos fármacos , Região Hipotalâmica Lateral/metabolismo , Receptores de Orexina/genética , Orexinas/genética , Orexinas/metabolismo , Ratos , Reflexo de Endireitamento/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/genética , Vigília/efeitos dos fármacos
19.
Curr Med Sci ; 39(4): 526-533, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31346986

RESUMO

Activation of macrophages is a key event for the pathogenesis of various inflammatory diseases. Notch signaling pathway recently has been found to be a critical pathway in the activation of proinflammatory macrophages. Salidroside (Sal), one of main bioactive components in Rhodiola crenulata (Hook. F. et Thoms) H. ohba, reportedly possesses anti-inflammatory activity and ameliorates inflammation in alcohol-induced hepatic injury. However, whether Sal regulates the activation of proinflammatory macrophages through Notch signaling pathway remains unknown. The present study investigated the effects of Sal on macrophage activation and its possible mechanisms by using both alcohol and lipopolysaccharide (LPS) to mimic the microenvironment of alcoholic liver. Detection of THP-1-derived macrophages exhibited that Sal could significantly decrease the expression of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß) and IL-6 in the macrophages at both mRNA and protein levels. Furthermore, Sal significantly suppressed NF-κB activation via Notch-Hes signaling pathway in a dose-dependent manner. Moreover, in the microenvironment of alcoholic liver, the expression of Notch-dependent pyruvate dehydrogenase phosphatase 1 (PDP1) was elevated, and that of M1 gene expression [inducible NO synthase (NOS2)] was up-regulated. These changes could all be effectively ameliorated by Sal. The aforementioned findings demonstrated that Sal could inhibit LPS-ethanol-induced activation of proinflammatory macrophages via Notch signaling pathway.


Assuntos
Glucosídeos/farmacologia , Inflamação/tratamento farmacológico , Fígado/efeitos dos fármacos , Fenóis/farmacologia , Rhodiola/química , Citocinas/genética , Etanol/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-6/genética , Lipopolissacarídeos/toxicidade , Fígado/lesões , Fígado/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , NF-kappa B/genética , Proteína Fosfatase 2C/genética , RNA Mensageiro/genética , Receptores Notch/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética
20.
BMC Pharmacol Toxicol ; 20(1): 38, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262364

RESUMO

BACKGROUND: This study aimed to examine femoral bone microstructure of mice after single and simultaneous administration to acrylamide and ethanol since both substances are often consumed separately and/or together by humans. Interactive effects of these toxins were analysed after one remodeling cycle. METHODS: Twenty clinically healthy adult mice were randomly divided into four groups following 2 weeks administration of toxins: A group - mice were fed with acrylamide (40 mg/kg bw); E group - mice were ethanol-fed (15% ethanol); AE group - mice were simultaneously fed with both toxins, and a C group - control (without acrylamide and/or ethanol supplementation). Generally, 2D and 3D imaging methods were used to determine cortical and trabecular bone tissues microstructure. Biochemical analyses of plasma parameters were also realized using commercially available ELISA tests and spectrophotometrically. RESULTS: Single and simultaneous exposure to acrylamide and ethanol affected only cortical bone microstructure. No significant changes in trabecular bone morphometry were detected among all groups. In mice from the A group, increased endocortical remodeling associated with a higher level of serum calcium and vasoconstriction of primary osteon's vascular canals (POVC) were identified. On the contrary, increased cortical porosity consistent with a decreased relative bone volume, bone mineral density (BMD) and lower levels of alkaline phosphatase (ALP), glutathione (GSH), calcium in plasma and also with vasodilation of POVC were observed in the E group. In the AE group, the highest density of secondary osteons associated with a lower BMD and decreased levels of ALP, GSH were documented. The parameters of POVC and Haversian canals approximated to the C group. In addition, single and simultaneous exposure to both toxins caused liver disease consistent with a higher values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in plasma of all experimental groups. CONCLUSIONS: Single administration to acrylamide and ethanol had negative effects on cortical bone structure of mice after one remodeling cycle. However, we identified possible antagonistic impact of these toxins on the structure of the cortical bone.


Assuntos
Acrilamida/toxicidade , Osso Cortical/efeitos dos fármacos , Etanol/toxicidade , Fêmur/efeitos dos fármacos , Animais , Remodelação Óssea , Osso Esponjoso/anatomia & histologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/efeitos dos fármacos , Osso Cortical/diagnóstico por imagem , Osso Cortical/patologia , Interações de Medicamentos , Fêmur/diagnóstico por imagem , Fêmur/patologia , Masculino , Camundongos , Microtomografia por Raio-X
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