RESUMEN
The aim of the present study was to assess the possible protective effect of γ-oryzanol (ORY) supplementation in a model of acute liver failure (ALF) induced by acetaminophen (APAP) in mice. Male Swiss strain mice were supplemented with ORY (10 and 50 mg/kg, per oral route) daily for 7 days. One hour after the last supplementation, animals received APAP (300 mg/kg, intraperitoneal). Twenty-four hours after APAP administration, mice were euthanized, and biochemical and histopathological determinations were performed. Histopathological analysis revealed that APAP caused vascular congestion, loss of cellular structure, and cellular infiltration in hepatocytes. Moreover, it caused oxidative damage (enzymatic and non-enzymatic analysis of oxidative stress), with loss of hepatic function leading to cell apoptosis (apoptotic parameters). ORY supplementation (ORY-10 and ORY-50) protected against all changes in ALF model. Thus, the protective effect of ORY supplementation was due to modulation of antioxidant defenses avoiding the apoptotic process.
Asunto(s)
Antioxidantes/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Apoptosis/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Fallo Hepático Agudo/prevención & control , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fenilpropionatos/farmacología , Acetaminofén , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Hígado/metabolismo , Hígado/patología , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/patología , Masculino , Ratones , Transducción de SeñalRESUMEN
INTRODUCTION AND OBJECTIVES: Acute liver failure (ALF) is a dramatic disorder requiring intensive care. MicroRNAs (miRNAs) have been identified to play important roles in ALF. This study was performed to identify miRNA-mRNA co-expression network after ALF to investigate the molecule mechanism underlying the pathogenesis of ALF. MATERIALS AND METHODS: The microarray dataset GSE62030 and GSE62029 were downloaded from Gene Expression Omnibus database. Overlapping differentially expressed miRNAs (DEmiRNAs) and genes (DEGs) were identified in liver tissues from patients with hepatitis B virus (HBV)-associated ALF in comparison with normal tissues from donors. Gene enrichment analysis was performed. Key pathways associated with the DEGs were identified. The miRNA-mRNA regulatory network was constructed. RESULTS: Total 42 DEmiRNAs and 523 DEGs were identified in liver tissues from patients with HBV-associated ALF. Gene ontology and pathways enrichment analysis showed upregulated DEGs were related to immune responses, inflammation, and infection, and downregulated DEGs were associated with amino acids, secondary metabolites and xenobiotics metabolism. In miRNA-mRNA co-expression network, DEGs were regulated by at least one DEmiRNA and transcription factor. Further analysis showed DEmiRNAs, including has-miR-55-5p, has-miR-193b-5p, has-miR-200b-3p, and has-miR-3175 were associated with amino acid metabolism, drug metabolism and detoxication, and signaling pathways including mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT, Ras, and Rap1. CONCLUSIONS: These miRNA-mRNA pairs and changed profiles were associated with and might be responsible for the impairment of detoxification and metabolism induced by HBV-associated ALF.
Asunto(s)
Redes Reguladoras de Genes , Hepatitis B/genética , Fallo Hepático Agudo/genética , MicroARNs/genética , ARN Mensajero/genética , Aminoácidos/metabolismo , Regulación de la Expresión Génica , Ontología de Genes , Hepatitis B/complicaciones , Hepatitis B/metabolismo , Humanos , Inactivación Metabólica/genética , Infecciones/genética , Inflamación/genética , Fallo Hepático Agudo/etiología , Fallo Hepático Agudo/metabolismo , Sistema de Señalización de MAP Quinasas/genética , Transducción de SeñalRESUMEN
INTRODUCTION AND OBJECTIVES: Acute liver failure (ALF) is a severe disease which is associated with a high mortality rate. As mild hypothermia has been shown to have protective effects on the brain, this study aimed to determine whether it also provides protection to the liver in rats with ALF and to explore its underlying mechanism. MATERIALS AND METHODS: In total, 72 rats were divided into 3 groups: control group (CG, treated with normal saline), normothermia group (NG, treated with d-galactosamine and lipopolysaccharide; d-GalN/LPS), and mild hypothermia group (MHG, treated with d-GalN/LPS and kept in a state of mild hypothermia, defined as an anal temperature of 32-35°C). The rats were examined at 4, 8, and 12h after treatment. RESULTS: Mild hypothermia treatment significantly reduced serum alanine transaminase and aspartate transaminase levels and improved the liver condition of rats with d-GalN/LPS-induced ALF at 12h. Serum tumor necrosis factor-alpha levels were significantly lower in the MHG than in the NG at 4h, but no significant differences were observed in the interleukin-10 levels between the NG and MHG at any time. The serum and hepatic levels of high mobility group box 1 were significantly lower in the MHG than in the NG at 8 and 12h. The protein expression levels of cytochrome C and cleaved-caspase 3 in hepatic tissues were significantly lower in the MHG than in the NG at 8h. CONCLUSION: Mild hypothermia improved the liver conditions of rats with ALF via its anti-inflammatory and anti-apoptotic effects.
Asunto(s)
Hipotermia Inducida/métodos , Fallo Hepático Agudo/terapia , Hígado/patología , Alanina Transaminasa/sangre , Animales , Apoptosis , Aspartato Aminotransferasas/sangre , Biomarcadores/metabolismo , Temperatura Corporal , Modelos Animales de Enfermedad , Femenino , Interleucinas/sangre , Hígado/metabolismo , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Intracranial hypertension and brain swelling are a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure (FHF). The pathogenesis of these complications has been investigated in man, in experimental models and in isolated cell systems. Currently, the mechanism underlying cerebral edema and intracranial hypertension in the presence of FHF is multi-factorial in etiology and only partially understood. The aim of this paper is to review the pathophysiology of cerebral hemodynamic and metabolism changes in FHF in order to improve understanding of intracranial dynamics complication in FHF.
Asunto(s)
Edema Encefálico/etiología , Circulación Cerebrovascular/fisiología , Hipertensión Intracraneal/etiología , Fallo Hepático Agudo/complicaciones , Edema Encefálico/fisiopatología , Encefalopatía Hepática/etiología , Encefalopatía Hepática/metabolismo , Encefalopatía Hepática/fisiopatología , Humanos , Hipertensión Intracraneal/fisiopatología , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/fisiopatologíaRESUMEN
ABSTRACT Intracranial hypertension and brain swelling are a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure (FHF). The pathogenesis of these complications has been investigated in man, in experimental models and in isolated cell systems. Currently, the mechanism underlying cerebral edema and intracranial hypertension in the presence of FHF is multi-factorial in etiology and only partially understood. The aim of this paper is to review the pathophysiology of cerebral hemodynamic and metabolism changes in FHF in order to improve understanding of intracranial dynamics complication in FHF.
RESUMO O edema cerebral e a hipertensão intracraniana (HIC) são as principais causas de morbidade e mortalidade de pacientes com insuficiência hepática fulminante (IHF). A patogênese dessas complicações tem sido investigada no homem, em modelos experimentais e em sistemas celulares isolados. Atualmente, o mecanismo subjacente ao edema cerebral e HIC na presença de IHF é multifatorial em etiologia e pouco compreendido na literatura. O objetivo deste trabalho é revisar a fisiopatologia das alterações hemodinâmicas e metabólicas cerebrais na IHF, visando melhorar a compreensão da complicação da hemodinâmica encefálica na IHF.
Asunto(s)
Humanos , Edema Encefálico/etiología , Circulación Cerebrovascular/fisiología , Fallo Hepático Agudo/complicaciones , Hipertensión Intracraneal/etiología , Edema Encefálico/fisiopatología , Encefalopatía Hepática/etiología , Encefalopatía Hepática/fisiopatología , Encefalopatía Hepática/metabolismo , Fallo Hepático Agudo/fisiopatología , Fallo Hepático Agudo/metabolismo , Hipertensión Intracraneal/fisiopatologíaRESUMEN
Hepatic encephalopathy (HE) represents a serious complication of acute liver failure (ALF) in which cerebral edema leading to brainstem herniation as a result of increased intracranial hypertension is a major consequence. Long non-coding RNAs (lncRNAs) play a significant role in coordinating gene expression, with recent studies indicating an influence in the pathogenesis of several diseases. To investigate their involvement in the cerebral pathophysiology of ALF, we profiled the expression of lncRNAs in the frontal cortex of mice at coma stage following treatment with the hepatotoxin azoxymethane. Of the 35,923 lncRNAs profiled using microarrays, 868 transcripts were found to be differentially expressed in the ALF-treated group compared to the sham control group. Of these, 382 lncRNAs were upregulated and 486 lncRNAs downregulated. Pathway analysis revealed these lncRNAs target a number of biological and molecular pathways that include cytokine-cytokine receptor interaction, the mitogen activated protein kinase signaling pathway, the insulin signaling pathway, and the nuclear factor-κB signaling pathway. False discovery rate adjustment identified 9 upregulated lncRNAs, 2 of which are associated with neuroepithelial transforming gene 1 (NET1) and the monocarboxylate transporter 2 (Slc16a7), potential contributors to astrocyte cytoskeletal disruption/swelling and lactate production, respectively. Our findings suggest an important role for lncRNAs in the brain in ALF in relation to inflammation, neuropathology, and in terms of the functional basis of HE. Further work on these non-coding RNAs may lead to new therapeutic approaches for the treatment and management of cerebral dysfunction resulting from this potentially life-threatening disorder.
Asunto(s)
Corteza Cerebral/metabolismo , Fallo Hepático Agudo/genética , ARN Largo no Codificante/metabolismo , Animales , Fallo Hepático Agudo/metabolismo , Masculino , Ratones Endogámicos C57BLRESUMEN
Acai has been used by the population due to its high nutritional value and its benefits to health, such as its antioxidant properties. The aim of this study was to evaluate the protective effect of acai frozen pulp on oxidative stress parameters in cerebral cortex, hippocampus and cerebellum of Wistar rats treated with carbon tetrachloride (CCl4). Thirty male Wistar rats (90-day-old) were orally treated with water or acai frozen pulp for 14 days (7 µL/g). On the 15th day, half of the animals received treatment with mineral oil and the other half with CCl4 (3.0 mL/kg). The cerebral cortex, hippocampus and cerebellum were dissected and used for analysis of creatine kinase activity (CK), thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, and the activity of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Statistical analysis was performed by ANOVA followed by Tukey's post-test. CCl4 was able to inhibit CK activity in all tissues tested and to provoke lipid damage in cerebral cortex and cerebellum, and protein damage in the three tissues tested. CCl4 enhanced CAT activity in the cerebral cortex, and inhibited CAT activity in the hippocampus and cerebellum and reduced SOD activity in all tissues studied. Acai frozen pulp prevented the inhibition of CK, TBARS, carbonyl and CAT activity in all brain structures and only in hippocampus for SOD activity. Therefore, acai frozen pulp has antioxidant properties and maybe could be useful in the treatment of some diseases that affect the central nervous system that are associated with oxidative damage.
Asunto(s)
Encéfalo/metabolismo , Euterpe , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/prevención & control , Estrés Oxidativo/fisiología , Extractos Vegetales/administración & dosificación , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Congelación , Frutas , Fallo Hepático Agudo/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: Pulmonary complications are common in acute liver failure (ALF). The role of the lungs in the uptake of harmful soluble endogenous macromolecules was evaluated in a porcine model of ALF induced by hepatic devascularization (n = 8) vs. controls (n = 8). In additional experiments, pulmonary uptake was investigated in healthy pigs. Fluorochrome-labeled modified albumin (MA) was applied to investigate the cellular uptake. RESULTS: As compared to controls, the ALF group displayed a 4-fold net increased lung uptake of hyaluronan, and 5-fold net increased uptake of both tissue plasminogen activator and lysosomal enzymes. Anatomical distribution experiments in healthy animals revealed that radiolabeled MA uptake (taken up by the same receptor as hyaluronan) was 53% by the liver, and 24% by the lungs. The lung uptake of LPS was 14% whereas 60% remained in the blood. Both fluorescence and electron microscopy revealed initial uptake of MA by pulmonary endothelial cells (PECs) with later translocation to pulmonary intravascular macrophages (PIMs). Moreover, the presence of PIMs was evident 10 min after injection. Systemic inflammatory markers such as leukopenia and increased serum TNF-α levels were evident after 20 min in the MA and LPS groups. CONCLUSION: Significant lung uptake of harmful soluble macromolecules compensated for the defect liver scavenger function in the ALF-group. Infusion of MA induced increased TNF-α serum levels and leukopenia, similar to the effect of the known inflammatory mediator LPS. These observations suggest a potential mechanism that may contribute to lung damage secondary to liver disease.
Asunto(s)
Células Endoteliales/metabolismo , Fallo Hepático Agudo/metabolismo , Lesión Pulmonar/metabolismo , Pulmón/metabolismo , Animales , Transporte Biológico , Modelos Animales de Enfermedad , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Ácido Hialurónico/metabolismo , Mediadores de Inflamación/sangre , Fallo Hepático Agudo/sangre , Fallo Hepático Agudo/complicaciones , Lesión Pulmonar/sangre , Lesión Pulmonar/etiología , Macrófagos Alveolares/metabolismo , Albúmina Sérica/metabolismo , Sus scrofa , Factores de TiempoRESUMEN
The aim of this study was to investigate if a protective effect from hypothyroidism in acute liver failure resulted from reduced endoplasmic reticulum stress and changes to the redox environment. Twenty male Sprague-Dawley rats were divided in four groups: (1) euthyroid (sham surgery), (2) hypothyroid, (3) euthyroid (sham surgery)+thioacetamide and (4) hypothyroid+thioacetamide. Hypothyroidism was confirmed two weeks after thyroidectomy, and thioacetamide (TAA) (400mg/kg, ip) was administrated to the appropriate groups for three days with supportive therapy. Grades of encephalopathy in all animals were determined using behavioral tests. Animals were decapitated and their blood was obtained to assess liver function. The liver was dissected: the left lobe was used for histology and the right lobe was frozen for biochemical assays. Body weight, rectal temperature and T4 concentration were lower in hypothyroid groups. When measurements of oxidative stress markers, redox environment, γ-glutamylcysteine synthetase and glutathione-S-transferase were determined, we observed that hypothyroid animals with TAA compensated better with oxidative damage than euthyroid animals treated with TAA. Furthermore, we measured reduced expressions of GADD34, caspase-12 and GRP78 and subsequently less hypothyroidism-induced cellular damage in hypothyroid animals. We conclude that hypothyroidism protects against hepatic damage caused by TAA because it reduces endoplasmic reticulum stress and changes to the redox environment.
Asunto(s)
Estrés del Retículo Endoplásmico , Hipotiroidismo/metabolismo , Fallo Hepático Agudo/metabolismo , Animales , Antígenos de Diferenciación/metabolismo , Caspasa 12/metabolismo , Retículo Endoplásmico/metabolismo , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Proteínas de Choque Térmico/metabolismo , Fallo Hepático Agudo/inducido químicamente , Masculino , Oxidación-Reducción , Estrés Oxidativo , Factores Protectores , Proteínas Proto-Oncogénicas/metabolismo , Ratas Sprague-DawleyRESUMEN
Background: The aging process promotes a progressive increase in chronic-degenerative diseases. The effect of these diseases on the functional capacity has been well recognized. Another health parameter concerns “quality of life related to health”. Among the elderly population, cardiovascular diseases stand out due to the epidemiological and clinical impact. Usually, these diseases have been associated with others. This set of problems may compromise both independence and quality of life in elderly patients who seek cardiologic treatment. These health parameters have not been well contemplated by cardiologists. Objective: Evaluating, among the elderly population with cardiovascular disease, which are the most relevant clinical determinants regarding dependence and quality of life. Methods: This group was randomly and consecutively selected and four questionnaires were applied: HAQ, SF-36, PRIME-MD e Mini Mental State. Results: The study included 1,020 elderly patients, 63.3% women. The group had been between 60 and 97 years-old (mean: 75.56 ± 6.62 years-old). 61.4% were independent or mild dependence. The quality of life total score was high (HAQ: 88.66 ± 2.68). 87.8% of patients had a SF-36 total score > 66. In the multivariate analysis, the association between diagnoses and high degrees of dependence was significant only for previous stroke (p = 0.014), obesity (p < 0.001), lack of physical activity (p = 0.016), osteoarthritis (p < 0.001), cognitive impairment (p < 0.001), and major depression (p < 0.001). Analyzing the quality of life, major depression and physical illness for depression was significantly associated with all domains of the SF-36. Conclusion: Among an elderly outpatient cardiology population, dependence and quality of life clinical determinants are not cardiovascular comorbidities, especially the depression. .
Fundamento: Com o envelhecimento, a prevalência de doenças crônico-degenerativas sofreu aumento progressivo. A repercussão dessas doenças sobre a capacidade funcional foi reconhecida. Outro parâmetro de saúde é a “qualidade de vida relacionada à saúde”. Na população idosa, as doenças cardiovasculares destacam-se pelo impacto epidemiológico e clínico. Elas, geralmente, vêm associadas a outras afecções. Esse conjunto de problemas pode comprometer a independência e a qualidade de vida do idoso que busca tratamento cardiológico. Objetivo: Avaliar, em uma população de idosos cardiopatas, quais são os determinantes clínicos mais relevantes de dependência e de qualidade de vida. Métodos: O grupo foi selecionado aleatória e consecutivamente, sendo aplicados quatro questionários: HAQ, SF-36, PRIME‑MD e Mini Exame do Estado Mental. Resultados: Incluiu-se 1020 idosos, 63,3% mulheres. O grupo tinha em média 75,56 ± 6,62 anos. 61,4% mostrou-se independente ou com dependência leve. O escore de qualidade de vida foi elevado (HAQ: 88,66 ± 2,68). 87,8% dos pacientes apresentou escore total do SF-36 ≥ 66. À análise multivariada, a associação entre os diagnósticos e graus elevados de dependência foi significante apenas para acidente vascular cerebral prévio (p = 0,014), obesidade (p < 0,001), sedentarismo (p = 0,016), osteoartrite (p < 0,001), déficit cognitivo (p < 0,001), e depressão maior (p < 0,001). Ao analisarmos a qualidade de vida, a depressão maior e a depressão por doença física associou-se significativamente com todos os domínios do SF-36. Conclusão: Em uma população de idosos cardiopatas, os determinantes clínicos mais relevantes de prejuízos para dependência e qualidade de vida foram as comorbidades não cardiovasculares, particularmente a depressão. .
Asunto(s)
Humanos , Hepatocitos/patología , Regeneración Hepática , Fallo Hepático Agudo/metabolismo , Apoptosis , /fisiología , Proteína Ligando Fas/fisiología , Hepatocitos/metabolismo , Fallo Hepático Agudo/terapia , Necrosis , Receptores del Factor de Necrosis Tumoral/metabolismo , Transducción de Señal , Ligando Inductor de Apoptosis Relacionado con TNF/fisiología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Hepatic involvement in primary amyloidosis is an infrequent challenge to the hepatologist. Although usually asymptomatic, amyloidosis may have unusual manifestations. Liver biopsy is an important diagnostic tool for this condition. Herein, we report three cases of portal hypertension related to primary hepatic amyloidosis, one of them in the form of acute liver failure.
Asunto(s)
Amiloidosis/complicaciones , Hipertensión Portal/etiología , Fallo Hepático Agudo/etiología , Anciano , Amiloidosis/metabolismo , Amiloidosis/patología , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Cadenas kappa de Inmunoglobulina/metabolismo , Hígado/patología , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/patología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/metabolismoRESUMEN
In this study, the authors evaluated the ability of diphenyl diselenide (PhSe)(2) to reverse acute hepatic failure induced by acetaminophen (APAP) in mice. The animals received an APAP dose of 600 mg/kg intraperitoneally (i.p.), and then 1 hour later, they received 15.6 mg/kg i.p. of (PhSe)(2). Three hours after (PhSe)(2) administration, the animals were sacrificed and blood and liver samples were collected for analysis. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG), thiobarbituric acid-reactive substances (TBARS), 2',7'-dichlorofluorescein (DFC), catalase activity (CAT), and myeloperoxidase (MPO) activity were determined in the liver. A methyl-tetrazolium reduction (MTT) assay was also performed on the liver. Histopathological studies were conducted in all groups. Exposure of animals to APAP induced oxidative stress, increased lipid peroxidation (LPO), and the generation of reactive species, reduced the levels of GSH, and caused an increase in the MPO activity. Treatment with (PhSe)(2) reduced LPO and the formation of reactive species and inhibited the processes of inflammation, reducing the hepatic damage induced by APAP. The results of this study show that (PhSe)(2) is a promising therapeutic option for the treatment of acute hepatic failure.
Asunto(s)
Acetaminofén/toxicidad , Derivados del Benceno/farmacología , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/prevención & control , Compuestos de Organoselenio/farmacología , Sustancias Protectoras/farmacología , Análisis de Varianza , Animales , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Histocitoquímica , Hígado/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Fallo Hepático Agudo/tratamiento farmacológico , Fallo Hepático Agudo/metabolismo , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Intestinal barrier dysfunction plays an important role in spontaneous bacterial peritonitis. In the present study, changes in the intestinal barrier with regard to levels of secretory immunoglobulin A (SIgA) and its components were studied in fulminant hepatic failure (FHF). Immunohistochemistry and double immunofluorescent staining were used to detect intestinal IgA, the secretory component (SC) and SIgA in patients with FHF (20 patients) and in an animal model with FHF (120 mice). Real-time PCR was used to detect intestinal SC mRNA in the animal model with FHF. Intestinal SIgA, IgA, and SC staining in patients with FHF was significantly weaker than in the normal control group (30 patients). Intestinal IgA and SC staining was significantly weaker in the animal model with FHF than in the control groups (normal saline: 30 mice; lipopolysaccharide: 50 mice; D-galactosamine: 50 mice; FHF: 120 mice). SC mRNA of the animal model with FHF at 2, 6, and 9 h after injection was 0.4 ± 0.02, 0.3 ± 0.01, 0.09 ± 0.01, respectively. SC mRNA of the animal model with FHF was significantly decreased compared to the normal saline group (1.0 ± 0.02) and lipopolysaccharide group (0.89 ± 0.01). The decrease in intestinal SIgA and SC induced failure of the intestinal immunologic barrier and the attenuation of gut immunity in the presence of FHF.
Asunto(s)
Animales , Humanos , Ratones , Inmunoglobulina A Secretora/inmunología , Fallo Hepático Agudo/inmunología , Estudios de Casos y Controles , Técnica del Anticuerpo Fluorescente , Inmunohistoquímica , Inmunidad Mucosa/inmunología , Inmunoglobulina A Secretora/metabolismo , Mucosa Intestinal/inmunología , Fallo Hepático Agudo/metabolismo , Ratones Endogámicos BALB C , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Intestinal barrier dysfunction plays an important role in spontaneous bacterial peritonitis. In the present study, changes in the intestinal barrier with regard to levels of secretory immunoglobulin A (SIgA) and its components were studied in fulminant hepatic failure (FHF). Immunohistochemistry and double immunofluorescent staining were used to detect intestinal IgA, the secretory component (SC) and SIgA in patients with FHF (20 patients) and in an animal model with FHF (120 mice). Real-time PCR was used to detect intestinal SC mRNA in the animal model with FHF. Intestinal SIgA, IgA, and SC staining in patients with FHF was significantly weaker than in the normal control group (30 patients). Intestinal IgA and SC staining was significantly weaker in the animal model with FHF than in the control groups (normal saline: 30 mice; lipopolysaccharide: 50 mice; D-galactosamine: 50 mice; FHF: 120 mice). SC mRNA of the animal model with FHF at 2, 6, and 9 h after injection was 0.4 ± 0.02, 0.3 ± 0.01, 0.09 ± 0.01, respectively. SC mRNA of the animal model with FHF was significantly decreased compared to the normal saline group (1.0 ± 0.02) and lipopolysaccharide group (0.89 ± 0.01). The decrease in intestinal SIgA and SC induced failure of the intestinal immunologic barrier and the attenuation of gut immunity in the presence of FHF.
Asunto(s)
Inmunoglobulina A Secretora/inmunología , Fallo Hepático Agudo/inmunología , Animales , Estudios de Casos y Controles , Técnica del Anticuerpo Fluorescente , Humanos , Inmunidad Mucosa/inmunología , Inmunoglobulina A Secretora/metabolismo , Inmunohistoquímica , Mucosa Intestinal/inmunología , Fallo Hepático Agudo/metabolismo , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Primary hepatic anaplastic large cell lymphoma (ALCL) of the liver is a rare entity. We present here two cases of primary hepatic anaplastic large cell lymphoma (ALCL) of the null-cell type. Both the cases had jaundice with "B" symptoms and hepatomegaly. The serum billirubin and liver enzymes were raised in both cases. The liver showed sinusoidal infiltration by atypical lymphoid cells with marked nuclear pleomorphism, dispersed chromatin and prominent nucleoli in both the cases. These cells were positive for CD30, negative for CD3, CD20 and EMA, and diagnosed as ALCL of the null-cell type. We hereby report these cases with the review of literature on primary hepatic ALCLwith their possible etio-pathogenesis & diagnostic clues which may help in timely diagnosis & management in such cases.
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Fallo Hepático Agudo/diagnóstico , Neoplasias Hepáticas/diagnóstico , Linfoma Anaplásico de Células Grandes/diagnóstico , Adulto , Bilirrubina/sangre , Biopsia , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Antígeno Ki-1/metabolismo , Hígado/enzimología , Hígado/patología , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Linfoma Anaplásico de Células Grandes/metabolismo , Linfoma Anaplásico de Células Grandes/patología , MasculinoRESUMEN
OBJECTIVE: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome resulting from liver failure. In the present study, we aimed to standardize an animal model of HE induced by thioacetamide (TAA) in C57BL/6 mice evaluating behavioral symptoms in association with liver damage and alterations in neurotransmitter release. METHOD: HE was induced by an intraperitoneal single dose of TAA (200 mg/kg, 600 mg/kg or 1,200 mg/kg). Behavioral symptoms were evaluated using the SHIRPA battery. Liver damage was confirmed by histopathological analysis. The glutamate release was measured using fluorimetric assay. RESULTS: The neuropsychiatric state, motor behavior and reflex and sensory functions were significantly altered in the group receiving 600 mg/kg of TAA. Biochemical analysis revealed an increase in the glutamate release in the cerebral cortex of HE mice. CONCLUSION: HE induced by 600 mg/kg TAA injection in C57BL/6 mice seems to be a suitable model to investigate the pathogenesis and clinical disorders of HE.
Asunto(s)
Conducta Animal/efectos de los fármacos , Encefalopatía Hepática/inducido químicamente , Fallo Hepático Agudo/inducido químicamente , Actividad Motora/efectos de los fármacos , Tioacetamida/toxicidad , Animales , Modelos Animales de Enfermedad , Ácido Glutámico/análisis , Fallo Hepático Agudo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
OBJECTIVE: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome resulting from liver failure. In the present study, we aimed to standardize an animal model of HE induced by thioacetamide (TAA) in C57BL/6 mice evaluating behavioral symptoms in association with liver damage and alterations in neurotransmitter release. METHOD: HE was induced by an intraperitoneal single dose of TAA (200 mg/kg, 600 mg/kg or 1,200 mg/kg). Behavioral symptoms were evaluated using the SHIRPA battery. Liver damage was confirmed by histopathological analysis. The glutamate release was measured using fluorimetric assay. RESULTS: The neuropsychiatric state, motor behavior and reflex and sensory functions were significantly altered in the group receiving 600 mg/kg of TAA. Biochemical analysis revealed an increase in the glutamate release in the cerebral cortex of HE mice. CONCLUSION: HE induced by 600mg/kg TAA injection in C57BL/6 mice seems to be a suitable model to investigate the pathogenesis and clinical disorders of HE.
OBJETIVO: A encefalopatia hepática (EH) é uma síndrome neuropsiquiátrica resultante da falência hepática. O objetivo do presente estudo foi estabelecer um modelo de EH induzida por tioacetamida (TAA) em camundongos C57BL/6 avaliando transtornos comportamentais, falência hepática e alterações na liberação de neurotransmissores. MÉTODO: A EH foi induzida por meio de uma única dose intraperitoneal de TAA (200 mg/kg, 600 mg/kg, 1.200 mg/kg). As alterações comportamentais foram avaliadas utilizando a bateria SHIRPA. A falência hepática foi confirmada através de análises histopatológicas e a liberação de glutamato medida, por ensaio fluorimétrico. RESULTADOS: Foram encontradas alterações significativas no estado neuropsiquiátrico, comportamento motor e função reflexa e sensorial no grupo que recebeu 600 mg/kg de TAA. Análises bioquímicas revelaram aumento na liberação de glutamato no córtex cerebral dos camundongos com EH. CONCLUSÃO: A EH induzida por 600 mg/kg de TAA em camundongos C57BL/6 parece ser um modelo apropriado para a investigação da patogênese e dos transtornos clínicos da EH.
Asunto(s)
Animales , Masculino , Ratones , Conducta Animal/efectos de los fármacos , Encefalopatía Hepática/inducido químicamente , Fallo Hepático Agudo/inducido químicamente , Actividad Motora/efectos de los fármacos , Tioacetamida/toxicidad , Modelos Animales de Enfermedad , Ácido Glutámico/análisis , Fallo Hepático Agudo/metabolismoRESUMEN
A morphological evaluation of histopathological liver samples from 42 fulminant hepatic failure cases from the Amazon Basin was undertaken in order to differentiate yellow fever (YF) from Lábrea hepatitis (LH) and other entities. The pattern and distribution of liver cell death as well as ballooning degeneration and midzonal apoptotic bodies were the most distinctive features of YF, whereas morula cells were the major finding for LH. Nineteen well characterised cases were further submitted to immunohistochemical studies for expression of YF antigen, hepatitis B surface antigen (HBsAg) and delta virus antigen. In both diseases, but particularly in LH, portal vein branch phlebitis was evident and might have played a role in the pathogenesis of hepatic injury, leading to hepatic extinction and portal tract approximation. The regeneration pattern was remarkable: a high proliferative index was detected in YF, whereas in LH multinucleation and pseudoacinar transformation, associated with portal type I collagen deposition and portal elastic fibre proliferation, was seen. In conclusion, midzonal apoptosis, portal phlebitis and a high proliferative index in patients without evidence of previous liver injury was the dominant picture in YF. On the other hand, LH cases showed extensive, predominantly lytic hepatocytic necrosis, portal and hepatic vein phlebitis and morula cells in patients with a morphological background of chronic liver disease.
Asunto(s)
Hepatitis Viral Humana/patología , Fallo Hepático Agudo/patología , Hígado/patología , Fiebre Amarilla/patología , Adolescente , Adulto , Brasil , Niño , Preescolar , Femenino , Hepatitis Viral Humana/inmunología , Humanos , Lactante , Fallo Hepático Agudo/metabolismo , Masculino , Fiebre Amarilla/inmunologíaRESUMEN
OBJECTIVE: Carbon tetrachloride (CCl4) is a lipid-soluble potent hepatotoxic; thus, it widely is used as an animal model of severe hepatic failure. Treatment with antioxidants may modulate the toxic effects of CCl4 on liver, generally with drug administration before CCl4, which can restrict its use in the clinical setting. We here describe the effects of N-acetylcysteine, deferoxamine, or both in the treatment of CCl4-induced hepatic failure. DESIGN: Prospective, randomized, controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats, weighing 200-250 g. INTERVENTIONS: Rats exposed to CCl4 were treated with N-acetylcysteine and/or deferoxamine or vehicle. MEASUREMENTS AND MAIN RESULTS: N-acetylcysteine plus deferoxamine treatment significantly attenuated hepatic and central nervous system oxidative damage after acute hepatic failure induced by CCl4. In addition, the serum levels of alanine aminotransferase, total bilirubin, and prothrombin time in the N-acetylcysteine plus deferoxamine group were significantly lower than those in the N-acetylcysteine or deferoxamine and saline groups. After N-acetylcysteine plus deferoxamine treatment, hepatocellular necrosis and inflammatory infiltration induced by carbon tetrachloride were greatly decreased. Survival in untreated rats was 5%. Survival increased to 25% and 35%, respectively, with N-acetylcysteine and deferoxamine treatment. In rats treated with N-acetylcysteine plus deferoxamine, survival was 80%. CONCLUSIONS: Our data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine reduces mortality rate, decreases oxidative stress, and limits inflammatory infiltration and hepatocyte necrosis induced by CCl4 in the rat.