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1.
Molecules ; 29(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38998903

RESUMO

The liver is the main organ responsible for the metabolism of ethanol, which suffers significantly as a result of tissue damage due to oxidative stress. It is known that C60 fullerenes are able to efficiently capture and inactivate reactive oxygen species in in vivo and in vitro systems. Therefore, the purpose of this study is to determine whether water-soluble C60 fullerene reduces the level of pathological process development in the liver of rats induced by chronic alcohol intoxication for 3, 6, and 9 months, depending on the daily dose (oral administration; 0.5, 1, and 2 mg/kg) of C60 fullerene throughout the experiment. In this context, the morphology of the C60 fullerene nanoparticles in aqueous solution was studied using atomic force microscopy. Such biochemical parameters of experimental animal blood as ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma-glutamyl transferase) and ALP (alkaline phosphatase) enzyme activities, CDT (carbohydrate-deficient transferrin) level, values of pro-antioxidant balance indicators (concentrations of H2O2 (hydrogen peroxide) and GSH (reduced glutathione), activities of CAT (catalase), SOD (superoxide dismutase) and GPx (selenium-dependent glutathione peroxidase)), and pathohistological and morphometric features of liver damage were analyzed. The most significant positive change in the studied biochemical parameters (up to 29 ± 2% relative to the control), as markers of liver damage, was recorded at the combined administration of alcohol (40% ethanol in drinking water) and water-soluble C60 fullerenes in the optimal dose of 1 mg/kg, which was confirmed by small histopathological changes in the liver of rats. The obtained results prove the prospective use of C60 fullerenes as powerful antioxidants for the mitigation of pathological conditions of the liver arising under prolonged alcohol intoxication.


Assuntos
Fulerenos , Fígado , Estresse Oxidativo , Animais , Fulerenos/farmacologia , Ratos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Intoxicação Alcoólica/tratamento farmacológico , Intoxicação Alcoólica/metabolismo , Ratos Wistar , Nanopartículas/química , Etanol/toxicidade
2.
Bull Exp Biol Med ; 177(1): 51-56, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38954302

RESUMO

The effectiveness of ethylmethylhydroxypyridine succinate (EMHPS) in acute alcohol intoxication was tested in a study on SPF male outbred ICR mice. Ethanol (concentration 40%) was administered to animals once intraperitoneally at a dose of 4 g/kg. Control animals were injected with saline in an equivalent volume. In 15 min after the administration of alcohol, the animals were injected intravenously or intramuscularly with EMHPS at a dose of 50 or 100 mg/kg or with saline via the same route in an equivalent volume. Animal behavior was tested 3 and 24 h later after administration of the substances. After 3 and 24 h, mice in the pathological control groups developed semiptosis, the gait and the turning over reflex were impaired, the strength of the hind limbs decreased and the distance between the hind limbs increased when landing; in the open-field test, the latency of the first movement increased, and the number of rearing postures decreased. Intravenous and intramuscular administration of EMHPS in doses of 50 and 100 mg/kg had a pronounced antitoxic and neuroprotective effect in acute alcohol intoxication: all studied parameters did not differ significantly from the control.


Assuntos
Intoxicação Alcoólica , Etanol , Camundongos Endogâmicos ICR , Piridinas , Animais , Masculino , Intoxicação Alcoólica/tratamento farmacológico , Camundongos , Piridinas/farmacologia , Piridinas/uso terapêutico , Injeções Intramusculares , Comportamento Animal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
3.
Int J Nanomedicine ; 19: 4907-4921, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828197

RESUMO

Purpose: Pueraria lobata (P. lobata), a dual-purpose food and medicine, displays limited efficacy in alcohol detoxification and liver protection, with previous research primarily focused on puerarin in its dried roots. In this study, we investigated the potential effects and mechanisms of fresh P. lobata root-derived exosome-like nanovesicles (P-ELNs) for mitigating alcoholic intoxication, promoting alcohol metabolism effects and protecting the liver in C57BL/6J mice. Methods: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pre-treated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers. Results: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (-31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation. Conclusion: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.


Assuntos
Intoxicação Alcoólica , Exossomos , Fígado , Camundongos Endogâmicos C57BL , Raízes de Plantas , Pueraria , Animais , Pueraria/química , Exossomos/metabolismo , Exossomos/efeitos dos fármacos , Exossomos/química , Camundongos , Masculino , Intoxicação Alcoólica/tratamento farmacológico , Raízes de Plantas/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Etanol/química , Etanol/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Alcoolismo/tratamento farmacológico , Isoflavonas
4.
J Ethnopharmacol ; 328: 118114, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38552993

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Alcohol misuse persists as a prevalent societal concern and precipitates diverse deleterious consequences, entailing significant associated health hazards including acute alcohol intoxication (AAI). Binge drinking, a commonplace pattern of alcohol consumption, may incite neurodegeneration and neuronal dysfunction. Clinicians tasked with managing AAI confront a dearth of pharmaceutical intervention alternatives. In contrast, natural products have garnered interest due to their compatibility with the human body and fewer side effects. Lingjiao Gouteng decoction (LGD), a classical traditional Chinese medicine decoction, represents a frequently employed prescription in cases of encephalopathy, although its efficacy in addressing acute alcoholism and alcohol-induced brain injury remains inadequately investigated. AIM OF THE STUDY: To investigate the conceivable therapeutic benefits of LGD in AAI and alcohol-induced brain injury, while delving into the underlying fundamental mechanisms involved. MATERIALS AND METHODS: We established an AAI mouse model through alcohol gavage, and LGD was administered to the mice twice at the 2 h preceding and 30 min subsequent to alcohol exposure. The study encompassed the utilization of the loss of righting reflex assay, histopathological analysis, enzyme-linked immunosorbent assays, and cerebral tissue biochemical assays to investigate the impact of LGD on AAI and alcohol-induced brain injury. These assessments included a comprehensive evaluation of various biomarkers associated with the inflammatory response and oxidative stress. Finally, RT-qPCR, Western blot, and immunofluorescence staining were carried out to explore the underlying mechanisms through which LGD exerts its therapeutic influence, potentially through the regulation of the RhoA/ROCK2/NF-κB signaling pathway. RESULTS: Our investigation underscores the therapeutic efficacy of LGD in ameliorating AAI, as evidenced by discernible alterations in the loss of righting reflex assay, pathological analysis, and assessment of inflammatory and oxidative stress biomarkers. Furthermore, the results of RT-qPCR, Western blot, and immunofluorescence staining manifest a noteworthy regulatory effect of LGD on the RhoA/ROCK2/NF-κB signaling pathway. CONCLUSIONS: The present study confirmed the therapeutic potential of LGD in AAI and alcohol-induced brain injury, and the protective effects of LGD against alcohol-induced brain injury may be intricately linked to the RhoA/ROCK2/NF-κB signaling pathway.


Assuntos
Intoxicação Alcoólica , Alcoolismo , Lesões Encefálicas , Camundongos , Humanos , Animais , NF-kappa B/metabolismo , Intoxicação Alcoólica/tratamento farmacológico , Transdução de Sinais , Etanol/farmacologia , Lesões Encefálicas/tratamento farmacológico , Biomarcadores , Quinases Associadas a rho/metabolismo
5.
Biomed Pharmacother ; 161: 114456, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36870283

RESUMO

Side effects of Ketoprofen and ketoprofen lysine salt (KLS) may be inter alia from the central nervous system, kidneys and liver. After binge drinking people often use ketoprofen, which increases the risk for the occurrence of side effects. The aim of the study was to compere effects of ketoprofen and KLS on the nervous system, kidneys and liver after ethyl alcohol intoxication. There were 6 groups of 6 male rats which received: ethanol; 0.9%NaCl; 0.9%NaCl and ketoprofen; ethanol and ketoprofen; 0.9%NaCl and KLS; ethanol and KLS. On day 2, the motor coordination test on a rotary rod and memory and motor activity test in the Y-maze were performed. Hot plate test was performed on day 6. After euthanasia brains, livers and kidneys were taken to histopathological tests. Motor coordination was significant worse in group 5 vs 1,3, p 0.05. Spontaneous motor activity of group 6 was significant better than that of groups 1,5. Pain tolerance of group 6 was significant worse than that of groups 1,4,5. Liver and kidney mass were significantly lower in group 6 vs group 3,5 and vs group 1,3, respectively. The histopathologic examination of the brains and kidneys revealed normal picture in all groups, without signs of inflammation. In the histopathologic examination of the livers in one animal in group 3 some of the specimens showed perivascular inflammation. After alcohol ketoprofen is a better painkiller than KLS. Spontaneous motor activity is better after KLS after alcohol. Both drugs have a similar effect on the kidneys and liver.


Assuntos
Intoxicação Alcoólica , Cetoprofeno , Masculino , Ratos , Animais , Cetoprofeno/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Ratos Wistar , Intoxicação Alcoólica/tratamento farmacológico , Cloreto de Sódio , Etanol/uso terapêutico , Inflamação/tratamento farmacológico , Cloreto de Sódio na Dieta , Fígado , Rim , Sistema Nervoso
6.
Food Funct ; 14(3): 1750-1760, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36727425

RESUMO

Various studies have reported that Noni shows various health effects. This study aimed to assess the ability of Noni fruit extract to serve as a single active functional ingredient for the alleviation of hangover symptoms in Sprague Dawley rats and healthy subjects in a single-dose, randomized, double-blind, crossover, placebo-controlled study. The rats were orally administered Noni fruit extract at 50 or 100 mg per kg body weight (B.W.) and HOVENIA. The blood ethanol (EtOH) and acetaldehyde concentrations were significantly lower in the 100 mg per kg B.W. group than in the EtOH group. Alcohol dehydrogenase and aldehyde dehydrogenase activity tended to increase in the 100 mg kg-1 B.W. group. In the human study, 30 subjects received either a placebo or Noni fruit extract (1 g). The Noni fruit extract group showed significantly faster time point at which the maximum concentration (Tmax) of alcohol than in the placebo group. In addition, blood acetaldehyde levels and diarrhea at 40 and 720 min after alcohol intake and the area under the curve between 40 and 60 min of acetaldehyde were significantly decreased in the Noni fruit extract group compared to the placebo group. According to the QUalitative INteraction Trees, subjects who were ≤36 years old who consumed more alcohol (>15 drinks per week) and had a higher total hangover score (>27.5 and 33) presented significantly lower blood acetaldehyde levels and less severe hangover symptoms. These results indicate that Noni fruit extract has the potential to improve hangover symptoms by decreasing alcohol and acetaldehyde levels.


Assuntos
Intoxicação Alcoólica , Morinda , Extratos Vegetais , Adulto , Animais , Humanos , Ratos , Acetaldeído , Intoxicação Alcoólica/tratamento farmacológico , Etanol/efeitos adversos , Frutas , Ratos Sprague-Dawley , Extratos Vegetais/uso terapêutico
8.
Blood Purif ; 52(3): 296-308, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36450226

RESUMO

BACKGROUND: Hemodialysis therapy has been used in the treatment of acute alcohol intoxication for many years, especially acute severe alcohol intoxication. OBJECTIVES: This study aimed to evaluate whether the combination of conventional treatment and naloxone with hemodialysis has advantages over conventional treatment and naloxone alone in patients with acute severe alcohol intoxication. METHODS: After searching 12 databases and 2 clinical trial centers. According to the established inclusion and exclusion criteria, the qualified literatures were screened. The outcome indicators were length of hospital stay, coma time, time of symptom disappearance, the overall complication rate, the incidence of pancreatitis, the incidence of aspiration pneumonia, the incidence of hepatic and renal dysfunction. Analysis was performed using Revman 5.3. RESULTS: This meta-analysis included 13 studies, including 932 subjects. In the treatment of acute severe alcohol intoxication, the use of hemodialysis on the basis of conventional treatment and naloxone could reduce the length of hospital stay (WMD = -15.16, 95% CI: -17.45 to -12.86, p < 0.001) in hours and (WMD = -4.89, 95% CI: -5.53 to -4.25, p < 0.001) in days; coma time (WMD = -5.43, 95% CI: -6.43 to -4.43, p < 0.001); time of symptom disappearance (WMD = -3.92, 95% CI: -5.37 to -2.47, p < 0.001); the overall complication rate (RR = 0.39, 95% CI: 0.28-0.55, p < 0.001); the incidence of pancreatitis (RR = 0.14, 95% CI: 0.05-0.43, p = 0.0006); the incidence of aspiration pneumonia (RR = 0.15, 95% CI: 0.04-0.66, p = 0.01), and the incidence of hepatic and renal dysfunction (RR = 0.21, 95% CI: 0.06-0.72, p = 0.01). CONCLUSIONS: It can be concluded that compared with the use of conventional treatment and naloxone alone, the use of hemodialysis on the basis of conventional treatment and naloxone for acute severe alcohol intoxication can reduce the length of hospital stay, coma time, time of symptom disappearance, and the incidence of some complications rate. Large scale, multicenter, and well-designed RCTs are needed in the future to prove our conclusions.


Assuntos
Intoxicação Alcoólica , Nefropatias , Pancreatite , Pneumonia Aspirativa , Humanos , Intoxicação Alcoólica/terapia , Intoxicação Alcoólica/tratamento farmacológico , Coma/terapia , Coma/tratamento farmacológico , Pancreatite/terapia , Diálise Renal , Pneumonia Aspirativa/tratamento farmacológico , Naloxona/uso terapêutico , Nefropatias/tratamento farmacológico , Estudos Multicêntricos como Assunto
10.
Clin Neuropharmacol ; 45(2): 21-26, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185146

RESUMO

ABSTRACT: The emergence of triptans represented a breakthrough in the treatment of migraine, but in clinical practice, patients describe symptoms that resemble those of a hangover after taking them. We propose the use of the Hangover Symptoms Scale (HSS) to evaluate this syndrome in patients that take triptans, which may help identify patients at higher risk of presenting these adverse effects that may interfere with therapeutic compliance.A cross-sectional observational pilot study with prospective data collection through a clinical-demographic questionnaire and the HSS was carried out on patients with migraine treated in headache units in 3 tertiary hospitals in Madrid.Sixty-six patients were included in the study. The median HSS was 4 and all symptoms were present in at least 15% of the patients, with difficulty to concentrate being the most frequent (57.6%). No significant differences were found between the presence of a higher HSS score and the sociodemographic characteristics of the patient or his migraine. The presence of aura was associated with a higher percentage of trembling (P = 0.029) and fatigue (nonvisual, polymodal auras; P = 0.017).According to our study, triptans are responsible for a set of symptoms overlapping with those that occur during a hangover. Therefore, we propose that the HSS could be a useful tool for the evaluation and quantification of these effects in patients receiving triptans. In addition, we found that clinical features could be more frequently associated with the appearance of these adverse effects that, however, are not related to any particular patient profile.


Assuntos
Intoxicação Alcoólica , Transtornos de Enxaqueca , Intoxicação Alcoólica/tratamento farmacológico , Estudos Transversais , Cefaleia/tratamento farmacológico , Humanos , Transtornos de Enxaqueca/diagnóstico , Triptaminas/efeitos adversos
11.
Molecules ; 27(4)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35208964

RESUMO

The purpose of this study is to evaluate the effect of the bioconversion products of Oenanthe javanica extract fermented by Lactiplantibacillus plantarum (OEFL) on relieving hangovers and improving liver function. In addition, the bioactive substance of the OEFL, which alleviates hangover and ethanol-induced liver damage, was identified and its bioactive property was verified through in vivo experiments. In major substances analysis using high-performance liquid chromatography, OEFL produced 9.5-fold higher p-coumaric acid than the O. Javanica extract (OE). In addition, considering that quinic acid, which is not present in the OE, was produced in the OEFL it was confirmed that chlorogenic acid was decomposed into quinic acid by bioconversion. In the in vivo experiment using Sprague-Dawley rats, the OEFL and p-coumaric acid diets reduced blood ethanol, acetaldehyde, GPT, and ALP concentrations, increasing blood albumin concentrations compared to ethanol-administered groups, demonstrating that OEFL and p-coumaric acid, the main substance in the OEFL, improved ethanol-induced liver damage. Furthermore, the OEFL and its main bioactive substance, p-coumaric acid, alleviated liver fibrosis by downregulating TGF-ß, SMAD-2, SMAD-4, α-SMA, and upregulating MMP-1. Therefore, OEFL is expected to be used as a functional food or pharmaceutical material as it has been confirmed to effectively relieve hangovers, prevent liver damage, and delay liver fibrosis in ethanol-induced liver damages.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Ácidos Cumáricos , Etanol/toxicidade , Lactobacillaceae/crescimento & desenvolvimento , Cirrose Hepática Alcoólica , Oenanthe/química , Extratos Vegetais , Intoxicação Alcoólica/metabolismo , Animais , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Cirrose Hepática Alcoólica/tratamento farmacológico , Cirrose Hepática Alcoólica/metabolismo , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley
12.
J Ethnopharmacol ; 282: 114593, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34480998

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication (AAI) is a ubiquitous emergency worldwide, whereas the searching for both effective and safe drugs is still a task to be completed. Modified Lvdou Gancao decoction (MLG), a traditional Chinese medicine decoction, has been confirmed to be valid to alcohol-induced symptoms and hepatotoxicity clinically, whereas its protective mechanisms have not been determined. MATERIALS AND METHODS: AAI mice model was established by alcohol gavage (13.25 mL/kg) and MLG (5, 10, 20 g/kg BW) was administered to mice 2 h before and 30 min after the alcohol exposure. Assay kits for alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamine transferase (GGT), total superoxide dismutase (T-SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidase (GSH-Px), as well as histopathology were used to explore the effects of MLG on acute alcohol-induced intoxication and hepatotoxicity. Mechanisms of MLG on oxidative stress and inflammatory were evaluated with RT-qPCR and Western Blot. RESULTS: MLG remarkably decreased the drunkenness rate, prolonged the tolerance time and shortened the sober-up time of AAI mice. After acute alcohol exposure, MLG treatment induced significant increment of ADH, ALDH, T-SOD and GSH-Px activities in liver, while serum ALT, AST, GGT and NO levels as well as hepatic MDA activity were reduced, in a dose-dependent manner. In contrast to the model group, the mRNA expression of TNFα, IL-1ß and NF-κB in the MLG treated groups had a downward trend while the Nrf-2 showed an upward trend simultaneously. Furthermore, the protein levels of p65, p-p65, p-IκBα in the MLG treated groups were considerably diminished, with HO-1 and Nrf2 elevated. To sum up, our results suggested that MLG could efficaciously ameliorate AAI via accelerating the metabolism of alcohol, alleviating acute hepatotoxicity, and weakening the oxidative stress coupled with inflammation response, which might be attributed to the inhibition of the NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway. CONCLUSIONS: Taken together, our present study verified the protective effect and mechanisms of MLG to AAI mice, and we further conclude that MLG may be a potent and reliable candidate for the prevention and treatment of AAI.


Assuntos
Intoxicação Alcoólica , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/farmacologia , Glycyrrhiza , Fator 2 Relacionado a NF-E2/metabolismo , Álcool Desidrogenase/metabolismo , Intoxicação Alcoólica/tratamento farmacológico , Intoxicação Alcoólica/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Monitoramento de Medicamentos/métodos , Heme Oxigenase-1/metabolismo , Testes de Função Hepática/métodos , Proteínas de Membrana/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos
13.
Daru ; 29(2): 367-376, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34709587

RESUMO

BACKGROUND: Toxic alcohol exposures are an ongoing concern in the United States. In the US, few studies characterize the local epidemiology of toxic alcohols over time. OBJECTIVES: The objective was to examine the incidence of toxic alcohol ingestions and changes in management over time. METHODS: This retrospective cohort study evaluates toxic alcohol ingestion phone calls to a regional poison center in the United States covering four states. Data were queried for this poison center from the National Poison Data System (NPDS) using generic codes for each toxic alcohol. Inclusion criteria were ingestion of toxic alcohol, age ≥ 13 years, from January 1, 2000 to Dec 31, 2017. Exclusion criteria were unrelated effects coded in the medical outcome, duplicate data, or incomplete demographic data. RESULTS: Of 926 subjects (adults and teenagers), 71.5% were male, and the mean age was 34.5 years. Toxic alcohol ingestion was more common in individuals younger than 40 years, with a significant relationship between age and intentional abuse or misuse (p = 0.001). There was also a significant relationship between age and reason for ingestion, with younger patients more likely to be suicidal (p < 0.001). Ethyleneglycol was the most common toxic alcohol. There was no change in the incidence of toxic alcohol ingestions over the study period. The mortality rate was 1.7%, and 31.2%of patients were hospitalized in a critical care unit. Major effects and death were more common in younger patients (p < 0.001). There was a significant difference in medical outcomes based on the type of toxic alcohol(p = 0.03). Fomepizole was the most common treatment. A Poisson regression model found no change in fomepizole use during the study period (p = 0.1). Ethanol administration over the study period increased (p = 0.02), while hemodialysis decreased (p = 0.02). CONCLUSION: Data obtained from a single regional United States poison center showed low mortality related to toxic alcohol ingestions. The most prevalent toxic alcohol was Ethylene glycol. In all cases, toxic alcohol ingestion was higher in the 20-29-year-old age group. Reasons for ingestion, in most cases, were suicidal. Fomepizole was the most common treatment, ethanol administration as an antidote is rising, and hemodialysis utilization is decreasing. Data may not be nationally representative.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Intoxicação Alcoólica/epidemiologia , Antídotos/uso terapêutico , Etilenoglicol/toxicidade , Fomepizol/uso terapêutico , Adolescente , Adulto , Fatores Etários , Intoxicação Alcoólica/etiologia , Intoxicação Alcoólica/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Centros de Controle de Intoxicações , Análise de Regressão , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
14.
Biomed Pharmacother ; 141: 111938, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34328086

RESUMO

INTRODUCTION: Ketoprofen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Side effects of ketoprofen occur mainly from the gastrointestinal tract due to the inhibition of cyclooxygenaze-1. Binge drinking at least once a week is reported by 80 million Europeans. On the day after many of them use NSAIDs. This increases the risk for damage of gastric mucosa. AIM: The aim of the study was to check if use of ketoprofen lysine salt (KLS) has any gastroprotective effect on mucosa of rat stomach after ethyl alcohol intoxication. MATERIALS AND METHODS: There were 6 groups of 6 male rats which received: RESULTS: In groups 1, 2 and 3 the histopathologic examination of the stomachs revealed normal picture, without signs of inflammation. In the group 4, 5 and 6 within the mucosa and submucosa there were visible numerous infiltrates of inflammatory cells, consisting mainly of lymphocytes, plasmocytes and eosinophilia. Total leukocyte count was elevated in group 3, 4, 6. There was a significant decrease of blood urea concentration in group 6 vs 2 and significant decrease of serum albumin in group 6 vs 1 and 2, and total protein vs group 1. CONCLUSION: Side effects of ketoprofen occur mainly from the gastrointestinal tract. KLS has no gastroprotective effect after ethanol-gastric injury and does not protect gastric mucosa from damage produced by binge drinking. Therefore it should not be used after drinking distilled spirits.


Assuntos
Intoxicação Alcoólica/patologia , Anti-Inflamatórios não Esteroides/toxicidade , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Cetoprofeno/análogos & derivados , Lisina/análogos & derivados , Intoxicação Alcoólica/tratamento farmacológico , Intoxicação Alcoólica/metabolismo , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Ciclo-Oxigenase 1/metabolismo , Mucosa Gástrica/metabolismo , Cetoprofeno/administração & dosagem , Cetoprofeno/toxicidade , Lisina/administração & dosagem , Lisina/toxicidade , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Ratos , Ratos Wistar
15.
AAPS PharmSciTech ; 22(3): 111, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33748928

RESUMO

Dihydromyricetin (DMY) is highly effective in counteracting acute alcohol intoxication. However, its poor aqueous solubility and permeability lead to the low oral bioavailability and limit its clinic application. The aim of this work is to use Solutol®HS15 (HS 15) as surfactant to develop novel micelle to enhance the oral bioavailability of DMY by improving its solubility and permeability. The DMY-loaded Solutol®HS15 micelles (DMY-Ms) were prepared by the thin-film hydration method. The particle size of DMY-Ms was 13.97 ± 0.82 nm with an acceptable polydispersity index of 0.197 ± 0.015. Upon entrapped in micelles, the solubility of DMY in water was increased more than 25-fold. The DMY-Ms had better sustained release property than that of pure DMY. In single-pass intestinal perfusion models, the absorption rate constant (Ka) and permeability coefficient (Papp) of DMY-Ms were 5.5-fold and 3.0-fold than that of pure DMY, respectively. The relative bioavailability of the DMY-Ms (AUC0-∞) was 205% compared with that of pure DMY (AUC0-∞), indicating potential for clinical application. After administering DMY-Ms, there was much lower blood alcohol level and shorter duration of the loss of righting relax (LORR) in drunk animals compared with that treated by pure DMY. In addition, the oral administration of DMY-Ms greatly reduced oxidative stress, and significantly defended liver and gastric mucosa from alcoholic damages in mice with alcohol-induced tissue injury. Taken together, HS 15-based micelle system greatly improves the bioavailability of DMY and represents a promising strategy for the management of acute alcoholism. Graphical abstract.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Flavonóis/administração & dosagem , Flavonóis/uso terapêutico , Intoxicação Alcoólica/patologia , Animais , Área Sob a Curva , Disponibilidade Biológica , Depressores do Sistema Nervoso Central/sangue , Etanol/sangue , Excipientes , Flavonóis/farmacocinética , Mucosa Gástrica/patologia , Hepatite Alcoólica/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Micelas , Nanopartículas , Equilíbrio Postural/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Tensoativos
16.
Bull Exp Biol Med ; 170(5): 631-635, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788110

RESUMO

The effect of a new derivative of GABA, the compound RGPU-260, on the heart contractility of rats exposed to chronic alcohol intoxication (10% ethanol solution for 24 weeks) was studied. In comparison with intact rats, the alcoholized ones were characterized with smaller increments in the rates of myocardial contraction (+dP/dtmax) and relaxation (-dP/dtmax), left ventricular pressure, and maximum intensity of functioning of structures during the load tests (volume load/preload, stimulation of the cardiac adrenergic receptors, and occlusion of the ascending aorta/afterload) attesting to degraded cardiac contractility function. In rats treated with RGPU-260 (daily, 25 mg/kg intragastrically during 14 days), these parameters were higher in comparison with control values indicating a positive action of the examined agent on inotropic function of the heart. Effectiveness of cardiotropic action of RGPU-260 was comparable to that of the reference drug mildronate.


Assuntos
Cardiotônicos/química , Cardiotônicos/farmacologia , Ácido gama-Aminobutírico/química , Ácido gama-Aminobutírico/farmacologia , Intoxicação Alcoólica/tratamento farmacológico , Animais , Feminino , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Ratos
18.
Am J Chin Med ; 49(1): 131-146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33371811

RESUMO

Alcoholic liver damage is caused by ethanol and its oxidized intermediates, and endotoxin-induced acute liver failure is mediated by apoptosis and inflammation. We investigated whether extracts of sprouts of Panax ginseng (SG) attenuate alcohol or endotoxin-induced acute liver injury in mice. Whole SG contains eight times more ginsenosides than the root and, because it grows quickly ([Formula: see text]30 days) without using pesticides, the whole-plant can be harvested. The extracts were enriched in phenolics and flavonoids and showed high radical scavenging activities. Mice received oral administration of SG or fermented SG (FSG) extracts 1 h before an injection of either ethanol or lipopolysaccharide and D-galactosamine (LPS/GalN). The latency of righting reflex was monitored to examine the effect of extracts on relieving hangover symptoms. The results indicate that FSG significantly reduced the latency of righting reflex, SG and FSG increased the activity and expression of ethanol-metabolizing enzymes, and FSG decreased hepatic necrosis and plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). During the ethanol metabolism, cytochrome P450 2E1 expression was increased, but 4-hydroxynonenal levels were decreased by the extracts due to their anti-oxidant activity. LPS/GalN-induced liver injury was reduced by SG and FSG; plasma ALT and AST levels, hepatic necrosis, and apoptotic and inflammatory markers were all decreased. In conclusion, SG extracts attenuated ethanol-induced hangover and endotoxin-induced acute liver injury, and fermentation enhanced the efficacy with regard to relieving hangover.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Fermentação , Flavonoides/análise , Panax/química , Fenóis/análise , Fitoterapia , Plântula/química , Administração Oral , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Sequestradores de Radicais Livres , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR
20.
Alcohol Alcohol ; 55(6): 660-666, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32808029

RESUMO

AIMS: Alcohol-related hangover symptoms: nausea, headache, stress and anxiety cause globally considerable amount of health problems and economic losses. Many of these harmful effects are produced by alcohol and its metabolite, acetaldehyde, which also is a common ingredient in alcohol beverages. The aim of the present study is to investigate the effect of the amino acid L-cysteine on the alcohol/acetaldehyde related aftereffects. METHODS: Voluntary healthy participants were recruited through advertisements. Volunteers had to have experience of hangover and/or headache. The hangover study was randomized, double-blind and placebo-controlled. Nineteen males randomly swallowed placebo and L-cysteine tablets. The alcohol dose was 1.5 g/kg, which was consumed during 3 h. RESULTS: The primary results based on correlational analysis showed that L-cysteine prevents or alleviates hangover, nausea, headache, stress and anxiety. For hangover, nausea and headache the results were apparent with the L-cysteine dose of 1200 mg and for stress and anxiety already with the dose of 600 mg. CONCLUSIONS: L-cysteine would reduce the need of drinking the next day with no or less hangover symptoms: nausea, headache, stress and anxiety. Altogether, these effects of L-cysteine are unique and seem to have a future in preventing or alleviating these harmful symptoms as well as reducing the risk of alcohol addiction.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Ansiedade/tratamento farmacológico , Cisteína/administração & dosagem , Cefaleia/tratamento farmacológico , Náusea/tratamento farmacológico , Vitaminas/administração & dosagem , Adulto , Intoxicação Alcoólica/complicações , Intoxicação Alcoólica/diagnóstico , Ansiedade/diagnóstico , Ansiedade/etiologia , Suplementos Nutricionais , Método Duplo-Cego , Cefaleia/diagnóstico , Cefaleia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/diagnóstico , Náusea/etiologia , Adulto Jovem
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