RESUMEN
SUMMARY: To investigate if the administration of boric acid (BA) would exert any protective effect against possible nephrotoxicity and hepatotoxicity induced by the exposure to acrylamide (ACR) in rats. In our study, we used a total of 28 rats that were divided into four equal groups. Group 1: the control group which was not treated with any procedure. Group 2: the ACR group that was administered ACR 50 mg/kg/day via intraperitoneal (i.p) route for 14 days. Group 3: the BA group that was administered BA 200 mg/kg/ day via gavage via peroral (p.o) route for 14 days. Group 4: the ACR+BA group that was administered BA simultaneously with ACR. Total antioxidant and oxidant (TAS/TOS) capacities were measured in all groups at the end of the experiment. In addition, the specimens obtained were evaluated with histopathological examination. Studies showed that the ACR and ACr+BA groups were not significantly different in terms of hepatic TAS level while the TOS level was higher in the ACR group than the ACR+BA group. The groups did not show any significant difference regarding renal TAS and TOS levels. In the histopathological examination of the hepatic tissue, the histopathological injury score of the ACR group was significantly higher than those of the other groups whereas it was significantly lower in the ACR+BA group than the ACR group. Our study concluded that Boric acid had a protective effect against acrylamide- induced hepatotoxicity, but not against nephrotoxicity.
El objetivo de este estudio fue investigar si la administración de ácido bórico (BA) ejercería algún efecto protector frente a la posible nefrotoxicidad y hepatotoxicidad inducida por la exposición a acrilamida (ACR) en ratas. En nuestro estudio, utilizamos un total de 28 ratas que se dividieron en cuatro grupos iguales. Grupo 1: grupo control que no fue tratado. Grupo 2: grupo ACR al que se le administró ACR 50 mg/kg/día por vía intraperitoneal (i.p) durante 14 días. Grupo 3: grupo BA al que se le administró BA 200 mg/kg/día por sonda por vía peroral (p.o) durante 14 días. Grupo 4: grupo ACR+BA al que se administró BA simultáneamente con ACR. Las capacidades antioxidantes y oxidantes totales (TAS/TOS) se midieron en todos los grupos al final del experimento. Además, los especímenes obtenidos fueron evaluados con examen histopatológico. Los estudios demostraron que los grupos ACR y ACr+BA no fueron significativamente diferentes en términos del nivel hepático de TAS, mientras que el nivel de TOS fue mayor en el grupo ACR que en el grupo ACR+BA. Los grupos no mostraron ninguna diferencia significativa con respecto a los niveles renales de TAS y TOS. En el examen histopatológico del tejido hepático, la puntuación de lesión histopatológica del grupo ACR fue significativamente mayor que la de los otros grupos, mientras que fue significativamente menor en el grupo ACR+BA que en el grupo ACR. Nuestro estudio concluyó que el ácido bórico tiene un efecto protector contra la hepatotoxicidad inducida por acrilamida, pero no contra la nefrotoxicidad.
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Animales , Ratas , Ácidos Bóricos/administración & dosificación , Acrilamida/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Lesión Renal Aguda/prevención & control , Bioquímica , Sustancias Protectoras/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Riñón/efectos de los fármacos , Riñón/fisiopatología , Hígado/efectos de los fármacos , Hígado/fisiopatologíaRESUMEN
PURPOSE: This study aimed to evaluate the effect and individual responsiveness after 12 (12wk) and 24 weeks (24wk) of physical exercise (PE) and nutritional guidance (NG) on metabolic syndrome (MetS) criteria and hepatic parameters in overweight adolescents. METHODS: The study comprised 94 overweight adolescents, aged between 10 and 16 years old, from both sexes, allocated into groups: PE and NG (PENGG, n = 64) and control with NG (NGCG, n = 30). Variables were collected at baseline, 12wk, and 24wk. Weight, height, abdominal circumference (AC), blood pressure, and peak oxygen consumption (VO2peak), as well as insulin, triglycerides (TAG), high-density lipoprotein (HDL-c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. HOMA-IR and QUICKI were calculated. PE session consisted of 45 min of indoor cycling, 45 min of walking, and 20 min of stretching, three times a week. The NG consisted of three collective sessions in the first 12wk. Anova, effect size, and prevalence of responders were used for statistical analysis. RESULTS: The PENGG12wk reduced anthropometric and metabolic measurements, while increased VO2peak and HDL-c. The PEG24wk promoted anthropometric, blood pressure, metabolic, and VO2peak improvements, but participants without PE returned to pre-exercise status and presented worsening AST and ALT concentrations. Frequencies of respondents in PENGG12wk versus (vs) NGCG12wk were, respectively, AC (69.1% vs 17.6%, p < 0.01), HDL-c (87.2% vs 23.5%, p < 0.01), TAG (67.3% vs 41.7%, p = 0.05) and ALT (45.5% vs 5,9%; p = 0.003). CONCLUSION: Interventions with PE were effective to reduce MetS components in 12wk and maintenance in 24wk, showing anthropometric, metabolic, and VO2peak improvements. Higher individual responses were observed in 12wk and in 24wk, important changes in overweight adolescent's therapy. LEVEL OF EVIDENCE: Level I, evidence obtained from well-designed controlled trials randomization. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Brazilian Registry of Clinical Trials (RBR-4v6h7b) and date of registration April 4th, 2020.
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Síndrome Metabólico/clasificación , Obesidad Infantil/complicaciones , Adolescente , Análisis de Varianza , Índice de Masa Corporal , Brasil/epidemiología , Niño , Femenino , Humanos , Hígado/anomalías , Hígado/metabolismo , Hígado/fisiopatología , Pruebas de Función Hepática/métodos , Pruebas de Función Hepática/estadística & datos numéricos , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Obesidad Infantil/sangre , Obesidad Infantil/epidemiología , Factores de Riesgo , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: This study investigated the effect of maternal obesity on aged-male offspring liver phenotype and hepatic expression of a programmed miRNA. METHODS: A mouse model (C57BL/6 J) of maternal diet-induced obesity was used to investigate fasting-serum metabolites, hepatic lipid content, steatosis, and relative mRNA levels (RT-PCR) and protein expression (Western blotting) of key components involved in hepatic and mitochondrial metabolism in 12-month-old offspring. We also measured hepatic lipid peroxidation, mitochondrial content, fibrosis stage, and apoptosis in the offspring. To investigate potential mechanisms leading to the observed phenotype, we also measured the expression of miR-582 (a miRNA previously implicated in liver cirrhosis) in 8-week-old and 12-month-old offspring. RESULTS: Body weight and composition was similar between 8-week-old offspring, however, 12-month-old offspring from obese mothers had increased body weight and fat mass (19.5 ± 0.8 g versus 10.4 ± 0.9 g, p < 0.001), as well as elevated serum levels of LDL and leptin and hepatic lipid content (21.4 ± 2.1 g versus 12.9 ± 1.8 g, p < 0.01). This was accompanied by steatosis, increased Bax/Bcl-2 ratio, and overexpression of p-SAPK/JNK, Tgfß1, Map3k14, and Col1a1 in the liver. Decreased levels of Bcl-2, p-AMPKα, total AMPKα and mitochondrial complexes were also observed. Maternal obesity was associated with increased hepatic miR-582-3p (p < 0.001) and miR-582-5p (p < 0.05). Age was also associated with an increase in both miR-582-3p and miR-582-5p, however, this was more pronounced in the offspring of obese dams, such that differences were greater in 12-month-old animals (-3p: 7.34 ± 1.35 versus 1.39 ± 0.50, p < 0.0001 and -5p: 4.66 ± 1.16 versus 1.63 ± 0.65, p < 0.05). CONCLUSION: Our findings demonstrate that maternal diet-induced obesity has detrimental effects on offspring body composition as well as hepatic phenotype that may be indicative of accelerated-ageing phenotype. These whole-body and cellular phenotypes were associated with age-dependent changes in expression of miRNA-582 that might contribute mechanistically to the development of metabolic disorders in the older progeny.
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Conducta Alimentaria/psicología , Hígado/metabolismo , Enfermedades Metabólicas/dietoterapia , Factores de Edad , Animales , Modelos Animales de Enfermedad , Femenino , Expresión Génica/fisiología , Hígado/fisiopatología , Exposición Materna/efectos adversos , Exposición Materna/estadística & datos numéricos , Enfermedades Metabólicas/etiología , Ratones , Ratones Endogámicos C57BL/metabolismo , Obesidad/complicaciones , Obesidad/dietoterapia , ARN MensajeroRESUMEN
Liver test abnormalities are frequently observed in patients with coronavirus disease 2019 (COVID-19) and are associated with worse prognosis. However, information is limited about pathological changes in the liver in this infection, so the mechanism of liver injury is unclear. Here we describe liver histopathology and clinical correlates of 27 patients who died of COVID-19 in Manaus, Brazil. There was a high prevalence of liver injury (elevated alanine aminotransferase and aspartate aminotransferase in 44% and 48% of patients, respectively) in these patients. Histological analysis showed sinusoidal congestion and ischemic necrosis in more than 85% of the cases, but these appeared to be secondary to systemic rather than intrahepatic thrombotic events, as only 14% and 22% of samples were positive for CD61 (marker of platelet activation) and C4d (activated complement factor), respectively. Furthermore, the extent of these vascular findings did not correlate with the extent of transaminase elevations. Steatosis was present in 63% of patients, and portal inflammation was present in 52%. In most cases, hepatocytes expressed angiotensin-converting enzyme 2 (ACE2), which is responsible for binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), even though this ectoenzyme was minimally expressed on hepatocytes in normal controls. However, SARS-CoV-2 staining was not observed. Most hepatocytes also expressed inositol 1,4,5-triphosphate receptor 3 (ITPR3), a calcium channel that becomes expressed in acute liver injury. Conclusion: The hepatocellular injury that commonly occurs in patients with severe COVID-19 is not due to the vascular events that contribute to pulmonary or cardiac damage. However, new expression of ACE2 and ITPR3 with concomitant inflammation and steatosis suggests that liver injury may result from inflammation, metabolic abnormalities, and perhaps direct viral injury.
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COVID-19/complicaciones , Hepatopatías/patología , Hepatopatías/virología , Hígado/patología , Hígado/virología , Adulto , Anciano , Anciano de 80 o más Años , Brasil , COVID-19/mortalidad , COVID-19/patología , COVID-19/fisiopatología , Femenino , Humanos , Hígado/fisiopatología , Hepatopatías/diagnóstico , Hepatopatías/fisiopatología , Pruebas de Función Hepática , Masculino , Persona de Mediana EdadRESUMEN
Zileuton is an inhibitor of the 5-lipoxygenase enzyme that transforms essential fatty acid (EFA) substrates into leukotrienes (LTB4, LTC4, LTD4 and LTE4), but little is known about the use of this drug in teleost fish. Therefore, the objective of this study was to evaluate the clinical safety of treatments with 2,25 mg and 4,50 mg of zileuton/Kg-1 (bodyweight), administered orally in the diet, through biochemical and hematological analysis during the acute inflammatory reaction in Nile tilapia (Oreochromis niloticus), induced by Aeromonas hydrophila bacterins. The study used eighty tilapias, conditioned in 20 tanks (n=4), constituting the following treatments: T0 (control), T1 (2,25 mg zileuton) and T2 (4,50 mg zileuton), being sampled eight animals per treatment in three periods: 6, 24 and 48 hours post-inoculation, and a 10th group consisting of fish without any type of stimulus to obtain the reference values. In order to evaluate and determine the blood count and serum biochemical, it was necessary to collect blood samples. The hematology results of the tilapia treated with zileuton did not reveal alterations between tilapia subjected to different treatments and control fish (T0). The liver cytotoxicity analysis of tilapias treated with zileuton did not reveal significant (p≥0,05) alterations in AST and ALT serum enzymatic activity. The study of tilapia blood total protein showed decrease in the T1 group at 48 HPI. As the treatment time progressed, the results indicated decrease in the serum albumin levels for T2 group at 24 HPI. The determination of serum biochemichal of creatinine, cholesterol, triglycerides, and glucose did not differ statistically between treatments. The results observed in the hematological and biochemical analyzes allows to conclude that zileuton administered orally, at doses of 2,25 and 4,50 mg/Kg-1 (body weight) demonstrated to be clinically safe.(AU)
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Animales , Aeromonas hydrophila , Cíclidos/sangre , Inhibidores de Proteína Activante de 5-Lipoxigenasa/administración & dosificación , Inflamación/tratamiento farmacológico , Hígado/fisiopatologíaRESUMEN
Functional enzyme assays to detect sublethal poisoning of Neotropical fish are paramount. Accordingly, we assayed a glutathione S-transferase (GST) activity in liver and kidney cytosols from Piaractus mesopotamicus injected with methyl parathion or benzo[a]pyrene using the substrate 1-chloro-2,4-dinitrobenzene (CDNB), which is the usual substrate for assaying a known general activity of GST. Since the most reactive substrate is required to reveal specific changes in enzyme activity, we also used two alternative substrates, 1,2-dichloro-4-nitrobenzene (DCNB) and ethacrynic acid (ETHA). Activities with CDNB or ETHA did not change. However, assays with DCNB showed that methyl parathion caused a decrease in GST activity in the liver on the 24th, 48th and 96th hour after the injection. DCNB also revealed that GST activity in the liver increased seven days after benzo[a]pyrene injection, coming down to normal after fourteen days. Benzo[a]pyrene, but not methyl parathion, increased the activities with DCNB in cytosol from the kidney seven and fourteen days after the injection. Thus, a decreased liver GST activity assayed with DCNB corresponded to contamination of P. mesopotamicus with methyl parathion. The increase of this GST activity in the liver and the kidney correlates to pacu contamination with polycyclic aromatic hydrocarbons.
Ensaios práticos de enzimas para detectar contaminação subletal de peixes neotropicais são da maior importância. Assim, ensaiamos a atividade da glutationa S-transferase (GST) em citosóis de fígado e de rim de Piaractus mesopotamicus injetados com metilparation ou benzo[a]pireno usando 1-cloro-2,4-dinitrobenzeno (CDNB), o substrato usual para ensaiar uma denominada atividade geral de GST. Desde que para indicar alterações na atividade de uma isoenzima, é necessário o substrato mais reativo, também usamos dois substratos alternativos, o 1,2-dicloro-4-nitrobenzeno (DCNB) e o ácido etacrínico (ETHA). As atividades com CDNB ou ETHA não mudaram. Entretanto, ensaios com DCNB mostraram que metilparation decresceu a atividade de GST no fígado em 24, 48 e 96 horas depois da injeção. O DCNB também revelou que sete dias depois da injeção de benzo[a]pireno a atividade da GST aumentou no fígado, normalizando depois de 14 dias. Benzo[a]pireno, mas não metilparation, aumentou as atividades com DCNB no citosol dos rins sete e 14 dias depois da injeção. Assim, uma atividade de GST ensaiada com DCNB diminuída no fígado correspondeu à contaminação de P. mesopotamicus com metilparation. O aumento dessa atividade de GST no fígado e nos rins está correlacionada com contaminação do pacu por hidrocarbonetos policíclicos aromáticos.
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Animales , Hidrocarburos Policíclicos Aromáticos/análisis , Gutatión-S-Transferasa pi/análisis , Characidae/fisiología , Hígado/fisiopatología , Metil Paratión/toxicidad , Contaminación del Agua/análisis , CitosolRESUMEN
The use of biological indicators has increased in recent years with the aim of investigating environ-mental pollution in aquatic environments that are vulnerable to the constant use of pesticides. Some biomarkers can help assess the health status, indicating physical, metabolic, and behavioral changes under acute and sublethal poisoning. The mixture of the active ingredients cyproconazole and pico-xystrobin is a widely used fungicide for the control of pests in cotton, rice, coffee, sugarcane, corn, soybean, and wheat. The objective of this study was to verify the occurrence of possible histopatholo-gical lesions in the liver and kidneys of bullfrog tadpoles (Lithobates catesbeianus) caused by a fungi-cide commercial formula composed of picoxystrobin and cyproconazole. The animals were subjected to different concentrations of the fungicide to determine the median lethal concentration (LC50-96h = 0.05 mg L-1), that is, the lethal dose for 50% of the animals in 96 h. After determining the value of LC50-96h, the animals were subjected to three sublethal concentrations (LC50-96h/2, LC50-96h/10, and LC-50-96h/100). Through histological biomarkers, it was verified that this fungicide changed the morphology of the animals' kidney and liver tissues in a chronic way, impairing the functioning of organs that are essential for their survival and metamorphosis, which can result in an imbalance in the biodiversity of aquatic ecosystems.(AU)
O uso de indicadores biológicos tem aumentado nos últimos anos, com o intuito de investigar a po-luição ambiental em ambientes aquáticos que são vulneráveis ao constante uso de pesticidas. Alguns biomarcadores podem ajudar a avaliar o estado de saúde, indicando alterações físicas, metabólicas e comportamentais de intoxicações agudas e subletais. A mistura dos ingredientes ativos picoxistrobina e ciproconazol é amplamente usada como fungicida para o controle de pragas da cultura de algodão, arroz, café, cana-de-açúcar, milho, soja e trigo. O objetivo deste trabalho foi verificar a ocorrência de possíveis lesões histopatológicas em fígado e rins de girinos de rã-touro (Lithobates catesbeianus) causadas pela mistura dos fungicidas picoxistrobina e ciproconazol. Os animais foram submetidos a diferentes concentrações do fungicida para determinação da concentração letal mediana (CL50-96h = 0,05 mg L-1), ou seja, a dose letal para 50% dos animais em 96 horas. Após a determinação do valor da CL50-96h, os animais foram submetidos a três concentrações subletais (CL50-96h/2, CL50-96h/10 e CL50-96h/100). Através dos biomarcadores histológicos, a pesquisa verificou que esse fungicida alterou a morfolo-gia dos tecidos renais e hepáticos dos animais de maneira crônica, prejudicando o funcionamento de órgãos que são fundamentais para sua sobrevivência e metamorfose, o que pode resultar em um desequilíbrio para a biodiversidade dos ecossistemas aquáticos.(AU)
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Animales , Plaguicidas/efectos adversos , Biomarcadores/análisis , Anfibios/anatomía & histología , Ecotoxicología , Riñón/fisiopatología , Hígado/fisiopatologíaRESUMEN
Abstract Thymoquinone (TQ) has shown hepatoprotective effects in various experimental studies. We aimed to investigate the possible beneficial effects of TQ regarding its prevention of alpha-amanitin induced hepatotoxicity in human C3A hepatocytes. After administering alpha-amanitin in a concentrations of 1 and 10µg/mL on the cells in a hepatocyte cell line, TQ was administered in various concentrations (10, 5, 1, 0.5, 0.1, 0.05, 0.01, 0.005 µg/mL). The MTT test was used to determine cell viability. For the groups given only TQ at various concentrations, the cell viability rates at 48 hours post-administration were found at 82.6, 98.3, 102.1, 102.5, 99.4, 99.4, 101.9 and 106.3%, respectively. For the group with 1μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates were found at 74.6, 88.5, 87.4, 88.7, 85.7, 86.8, 88.4, and 92.9%, respectively. For the group with 10μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates for each TQ subgroup were found at 65.2, 79.2, 81.4, 81.1, 81.8, 81.8, 82.2 and 91.9%, respectively. Our study is the first in vitro study that investigates TQ's effects on alpha-amanitin induced hepatotoxicity. Although TQ had beneficial effect in low doses did not significantly increase cell viability in liver damage due to alpha-amanitin toxicity.
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Línea Celular/clasificación , Técnicas In Vitro/métodos , Alfa-Amanitina/administración & dosificación , Hígado/fisiopatologíaRESUMEN
Introducción: La hamartomatosis biliar múltiple o también llamada enfermedad de los complejos de von Meyenburg fue descrita por este autor en 1955. Tiene un origen disembriogénico con un curso evolutivo benigno y asintomático, con pruebas funcionales hepáticas normales. Por los estudios de imágenes se puede confirmar el diagnóstico, pero igualmente ante un hígado multinodular pueden diagnosticar una hepatopatía crónica sin precisar su etiología, por lo que es imprescindible el diagnóstico histológico con biopsia hepática translaparoscópica dirigida. No se necesita ningún tratamiento específico y su seguimiento es ecográfico semestral o anual. Objetivo: Presentar el valor de la biopsia hepática dirigida por laparoscopia a las lesiones por hamartomatosis biliar múltiple. Desarrollo: Se presenta un paciente de 53 años con antecedentes de ser un bebedor social con frecuencia semanal. Ingresa por fiebre asociada a una sepsis urinaria, en el que aparece un fortuito hallazgo ecográfico de un hígado multinodular, sin precisar un diagnóstico etiológico por otros estudios de imágenes. Esto motivó a realizarle una laparoscopia con toma de biopsia hepática dirigida a las lesiones observadas. Se confirma el diagnóstico histológico de esta entidad. Conclusiones: Se demostró la importancia y vigencia del valor diagnóstico de la laparoscopia, al igual que la biopsia hepática dirigida para lograr el diagnóstico histológico de certeza en esta entidad(AU)
Introduction: Multiple biliary hamartomatosis or von Meyenburg complex disease was described by this author in 1955. Its origin is dysembryogenic with a benign and asymptomatic evolutionary course, with normal liver function tests. Imaging studies can confirm the diagnosis, but likewise, when it is a multinodular liver, chronic liver disease can be diagnosed without specifying its etiology, which is why it is essential a histological diagnosis with a directed overlaparoscopic liver biopsy. No specific treatment is needed and its follow-up is semi-annual or annual ultrasound. Objective: To present the value of laparoscopically directed liver biopsy for multiple biliary hamartomatosis lesions. Case report: A 53-year-old patient with a history of being a social drinker with a weekly frequency is reported. He was admitted for fever associated with urinary sepsis, in which a fortuitous ultrasound finding of a multinodular liver appeared, without requiring an etiological diagnosis by other imaging studies. This led to a laparoscopy with a liver biopsy aimed at the observed lesions. The histological diagnosis of this entity is confirmed. Conclusions: The importance and validity of the diagnostic value of laparoscopy, as well as directed liver biopsy to achieve a certain histological diagnosis in this entity, was demonstrated(AU)
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Humanos , Masculino , Persona de Mediana Edad , Biopsia/métodos , Síndrome de Hamartoma Múltiple/epidemiología , Laparoscopía/métodos , Hígado/fisiopatologíaRESUMEN
Several studies have sought new therapies for obesity and liver diseases. This study investigated the effect of the trypsin inhibitor isolated from tamarind seeds (TTI), nanoencapsulated in chitosan and whey protein isolate (ECW), on the liver health status of the Wistar rats fed with a high glycemic index (HGLI) diet. The nanoformulations without TTI (CW) and ECW were obtained by nanoprecipitation technique, physically and chemically characterized, and then administered to the animals. The adult male Wistar rats (n = 20) were allocated to four groups: HGLI diet + water; standard diet + water; HGLI diet + ECW (12.5 mg/kg); and HGLI diet + CW (10.0 mg/kg), 1 mL per gagave, for ten days. They were evaluated using biochemical and hematological parameters, Fibrosis-4 Index for Liver Fibrosis (FIB-4), AST to Platelet Ratio Index (APRI) scores, and liver morphology. Both nanoparticles presented spherical shape, smooth surface, and nanometric size [120.7 nm (ECW) and 136.4 nm (CW)]. In animals, ECW reduced (p < 0.05) blood glucose (17%), glutamic oxalacetic transaminase (39%), and alkaline phosphatase (24%). Besides, ECW reduced (p < 0.05) APRI and FIB-4 scores and presented a better aspect of hepatic morphology. ECW promoted benefits over a liver injury caused by the HGLI diet.
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Quitosano/química , Dieta , Índice Glucémico , Hígado/lesiones , Nanopartículas/química , Tamarindus/química , Inhibidores de Tripsina/farmacología , Proteína de Suero de Leche/química , Animales , Glucemia/metabolismo , Ayuno/sangre , Homeostasis , Insulina/sangre , Resistencia a la Insulina , Riñón/fisiopatología , Hígado/efectos de los fármacos , Hígado/patología , Hígado/fisiopatología , Masculino , Nanopartículas/ultraestructura , Ratas Wistar , Valores de ReferenciaRESUMEN
Liver ischemia-reperfusion injury (IRI) is a phenomenon inherent to hepatic surgery that severely compromises the organ functionality, whose underlying mechanisms involve cellular and molecular interrelated processes leading to the development of an excessive inflammatory response. Liver resident cells and those recruited in response to injury generate pro-inflammatory signals such as reactive oxygen species, cytokines, chemokines, proteases and lipid mediators that contribute to hepatocellular necrosis and apoptosis. Besides, dying hepatocytes release damage-associated molecular patterns that actívate inflammasomes to further stimulate inflammatory responses leading to massive cell death. Since liver IRI is a complication of hepatic surgery in man, extensive preclinical studies have assessed potential protective strategies, including the supplementation with natural compounds, with the objective to downregulate nuclear factor-κB functioning, the main effector of inflammatory responses. This can be accomplished by either the activation of peroxisome proliferator-activated receptor-α, G protein-coupled receptor 120 or antioxidant signaling pathways, the synthesis of specific pro-resolving mediators, downregulation of Toll-like receptor 4 activity or additional contributory mechanisms that are beginning to be understood. The latter aspect is a crucial issue to be accomplished in preclinical studies, in order to establish adequate conditions for the supplementation with natural products before major liver surgeries in man involving warm IR, such as hepatic trauma or resection of large intrahepatic tumors.
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Productos Biológicos/uso terapéutico , Ácidos Grasos Insaturados/uso terapéutico , Hígado/irrigación sanguínea , Alcohol Feniletílico/análogos & derivados , Daño por Reperfusión/prevención & control , Daño por Reperfusión/terapia , Vitaminas/uso terapéutico , Animales , Ácido Ascórbico/uso terapéutico , Humanos , Hígado/fisiopatología , Alcohol Feniletílico/uso terapéutico , Daño por Reperfusión/fisiopatología , Vitamina E/uso terapéuticoRESUMEN
Dengue (DEN) is the most prevalent arbovirus among humans, and four billion people live at risk of infection. The clinical manifestations of DEN are variable, and the disease may present subclinically or asymptomatically. A quarter of patients develop classical dengue (CD) or severe dengue (SD), which is potentially lethal and involves vascular permeability changes, severe hemorrhage and organ damage. The involvement of the liver is a fairly common feature in DEN, and alterations range from asymptomatic elevation of transaminases to acute liver failure. Since its introduction in Brazil in 1990, two strains of Dengue virus (DENV) serotype 2 (DENV-2) have been detected: Lineage I, which is responsible for an outbreak in 1991, and Lineage II, which caused an epidemic greater than the previous one and had a different epidemiological profile. To date, studies on different strains of the same serotype/genotype and their association with disease severity are scarce. In addition, one of the greatest challenges regarding the study of DEN pathogenesis and the development of drug and vaccine therapies is the absence of an animal model that reproduces the disease as it occurs in humans. The main goals of this study were to assess BALB/c mouse susceptibility experimentally infected by two distinct DENV-2 strains and characterize possible differences in the clinical signs and alterations induced in the liver resulting from those infections. Mice infected by the two DENV-2 lineages gained less weight than uninfected mice; however, their livers were slightly heavier. Increased AST and AST levels were observed in infected mice, and the number of platelets increased in the first 72 h of infection and subsequently decreased. Mice infected with both lineages presented leukocytosis but at different times of infection. The histopathological changes induced by both lineages were similar and comparable to the changes observed in DEN fatal cases. The viral genome was detected in two liver samples. The results demonstrate the susceptibility of BALB/c mice to both DENV-2 lineages and suggest that the changes induced by those strains are similar, although for some parameters, they are manifested at different times of infection.
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Virus del Dengue/patogenicidad , Hígado/virología , Animales , Temperatura Corporal , Peso Corporal , Virus del Dengue/clasificación , Modelos Animales de Enfermedad , Inmunocompetencia , Hígado/fisiopatología , Pruebas de Función Hepática , Ratones , Ratones Endogámicos BALB C , Tamaño de los ÓrganosRESUMEN
Sickle cell disease (SCD) is caused by a homozygous mutation in the ß-globin gene, which leads to erythrocyte sickling, vasoocclusion, and intense hemolysis. P-selectin inhibition has been shown to prevent vasoocclusive events in patients with SCD; however, the chronic effect of P-selectin inhibition in SCD remains to be determined. Here, we used quantitative liver intravital microscopy in our recently generated P-selectin-deficient SCD mice to show that chronic P-selectin deficiency attenuates liver ischemia but fails to prevent hepatobiliary injury. Remarkably, we find that this failure in resolution of hepatobiliary injury in P-selectin-deficient SCD mice is associated with the increase in cellular senescence and reduced epithelial cell proliferation in the liver. These findings highlight the importance of investigating the long-term effects of chronic P-selectin inhibition therapy on liver pathophysiology in patients with SCD.
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Anemia de Células Falciformes/patología , Isquemia/patología , Hígado/irrigación sanguínea , Selectina-P/deficiencia , Anemia de Células Falciformes/fisiopatología , Animales , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/patología , Senescencia Celular , Células Epiteliales/patología , Hemo-Oxigenasa 1/análisis , Hemólisis , Hígado/patología , Hígado/fisiopatología , Proteínas de la Membrana/análisis , Ratones , Ratones Noqueados , Modelos Animales , Selectina-P/genéticaRESUMEN
BACKGROUND: Besides the clinical benefit of crizotinib in ALK-rearranged metastatic non-small cell lung cancer (NSCLC), concerns about its hepatotoxicity have arisen. It is not clear whether this is a drug class side effect or if the use of other selective ALKs inhibitors is safe after this serious adverse event. While evidence from clinical trials is scarce, reports of treatment after crizotinib-induces hepatitis may add to clinical decision. CASE PRESENTATION: Herein, we report a case of acute hepatitis induced by crizotinib in a 32-years-old female diagnosed with metastatic NSCLC, harboring the ALK-rearrangement. After 60 days of crizotinib therapy, the patient presented with acute hepatitis, diagnosed after investigation of non-specific symptoms, such as nausea and fatigue. Serum aspartate aminotransferase and alanine aminotransferase levels had increased from baseline to 3010 IU/L and 9145 IU/L, respectively. Total bilirubin increased up to 7.91 mg/dL, but she did not develop liver failure. After crizotinib discontinuation, a gradual hepatic function recovery occurred. Unfortunately, during the period without specific oncology treatment, her disease showed an unequivocal progression. Therefore, she started on alectinib with great response, and no liver function alteration recurred. CONCLUSIONS: This case suggests that alectinib, even belonging to the same drug class, could be used as an alternative agent when crizotinib is the etiology of liver damage, but more robust evidence has awaited.
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Carbazoles/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Crizotinib/efectos adversos , Hepatitis/etiología , Neoplasias Pulmonares/tratamiento farmacológico , Piperidinas/uso terapéutico , Adulto , Bilirrubina/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Hepatitis/tratamiento farmacológico , Humanos , Hígado/efectos de los fármacos , Hígado/fisiopatología , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) affects ~25% of world population and cases have increased in recent decades. These anomalies have several etiologies; however, obesity and metabolic dysfunctions are the most relevant causes. Despite being considered a public health problem, no effective therapeutic approach to treat NAFLD is available. For that, a deep understanding of metabolic routes that support hepatic diseases is needed. AREAS COVERED: This review covers aspects of the onset of NAFLD. Thereby, biochemistry routes as well as cellular and metabolic effects of the gut microbiota in body's homeostasis and epigenetics are contextualized. EXPERT OPINION: Recently, the development of biological sciences has generated innovative knowledge, bringing new insights and perspectives to clarify the systems biology of liver diseases. A detailed comprehension of epigenetics mechanisms will offer possibilities to develop new therapeutic and diagnostic strategies for NAFLD. Different epigenetic processes have been reported that are modulated by the environment such as gut microbiota, suggesting strong interplays between cellular behavior and pathology. Thus, a more complete description of such mechanisms in hepatic diseases will help to clarify how to control the establishment of fatty liver, and precisely describe molecular interplays that potentially control NAFLD.
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Metabolismo de los Lípidos/fisiología , Hígado/fisiopatología , Enfermedades Metabólicas/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Epigenómica , Microbioma Gastrointestinal/fisiología , Humanos , Enfermedades Metabólicas/complicaciones , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/genética , Obesidad/complicaciones , Obesidad/fisiopatologíaRESUMEN
Cigarette smoke is highly toxic, and it can promote increased production of reactive species and inflammatory response and leads to liver diseases. Quercetin is a flavonoid that displays antioxidant and anti-inflammatory activities in liver diseases. This study aimed at evaluating the protective effects of quercetin on livers from mice exposed to long-term cigarette smoke exposure. Male C57BL/6 mice were divided into five groups: control (CG), vehicle (VG), quercetin (QG), cigarette smoke (CSG), quercetin, and cigarette smoke (QCSG). CSG and QCSG were exposed to cigarette smoke for sixty consecutive days; at the end of the exposures, all animals were euthanized. Mice that received quercetin daily and were exposed to cigarette smoke showed a reduced influx of inflammatory cells, oxidative stress, inflammatory reaction, and histopathological changes in the liver, compared to CSG. These results suggest that quercetin may be an effective adjuvant for treating damage to the liver due to cigarette smoke exposure.
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Fumar Cigarrillos/efectos adversos , Hígado/patología , Sustancias Protectoras/farmacología , Quercetina/farmacología , Animales , Antioxidantes/farmacología , Biomarcadores/metabolismo , Peso Corporal , Mediadores de Inflamación/metabolismo , Hígado/efectos de los fármacos , Hígado/fisiopatología , Pruebas de Función Hepática , Masculino , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacosRESUMEN
OBJECTIVES: Vascular and biliary complications associated with liver transplants involve high morbidity and mortality as well as cost overrun for health systems. Efforts to prioritize their prevention require not only clinical information but also information on costs that reflect the economic burden on health systems. The objective of this study was to describe cost overrun incurred from early vascular and biliary complications after liver transplant. METHODS: This cases series included liver transplant patients treated at the San Vicente Foundation University Hospital, Rionegro, Antioquia, from January 1, 2013, to December 31, 2018. All liver transplant patients treated during the above period were included; the absence of clinical records on the variables of interest was considered the exclusion criterion. A probabilistic analysis of patient cost was performed. Monte Carlo simulations as well as a 1-way sensitivity analysis per transplant cost component were performed. RESULTS: Records from 154 patients were assessed. The average patient age was 56.9 (SD 10.9) years; 42.9% of patients were women. Of all, 36.4% patients were classified as Child C, and the average Model for End-Stage Liver Disease score was 19.6. The average cost for patients without complications was $27 834.82, whereas that for patients with early vascular complications was $36 747.83 and for those with early biliary complications was $38 523.74. CONCLUSION: Early vascular and biliary complications after liver transplant increase healthcare costs, with the increase being significant in patients with biliary complications.
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Enfermedades de las Vías Biliares/etiología , Costos de la Atención en Salud/normas , Trasplante de Hígado/efectos adversos , Enfermedades Vasculares/etiología , Anciano , Enfermedades de las Vías Biliares/economía , Enfermedades de las Vías Biliares/epidemiología , Colombia/epidemiología , Femenino , Costos de la Atención en Salud/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Humanos , Hígado/fisiopatología , Trasplante de Hígado/economía , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Vasculares/economía , Enfermedades Vasculares/epidemiologíaRESUMEN
BACKGROUND: Modern imaging plays a central role in the care of obese patients, and there is an integral focus on its use and accessibility in individuals who have alterations of various in various organs. The objective in this study was to perform an echographic analysis of musculoskeletal system disorders, endothelial dysfunction and the left ventricle (LV) in obese rats. METHODS: Sprague Dawley rats (250 ± 5 g) were obtained and divided into two groups: the control (C) group was fed with a standard diet, and the obese (Ob) group was fed hyper caloric diet with a high fructose-fat content for 4 months. Body weight, cholesterol, triglycerides, glucose, inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1) were measured. Additionally, two-dimensional echocardiography, abdominal ultrasound and musculoskeletal system studies were performed in the lower extremities. RESULTS: The body weight in the Ob group was increased compared to that in the control group, (p < 0.001); in addition, increased glucose, cholesterol and triglyceride concentrations (p < 0.05) as well as increased levels of the adhesion molecules ICAM-1 and, VCAM-1 (p < 0.01) were found in the Ob group vs the C group. On ultrasound, 75% of the Ob group presented fatty liver and distal joint abnormalities. CONCLUSION: Obese rats exhibit endothelial dysfunction and musculoskeletal changes, also, fatty liver and articular cysts in the posterior region of the distal lower- extremity joints.
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Endotelio Vascular/diagnóstico por imagen , Corazón/diagnóstico por imagen , Hígado/diagnóstico por imagen , Sistema Musculoesquelético/diagnóstico por imagen , Obesidad/diagnóstico , Anatomía Transversal , Animales , Endotelio Vascular/patología , Endotelio Vascular/fisiopatología , Corazón/fisiopatología , Molécula 1 de Adhesión Intercelular/metabolismo , Hígado/fisiopatología , Masculino , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/etiología , Enfermedades Musculoesqueléticas/patología , Enfermedades Musculoesqueléticas/fisiopatología , Sistema Musculoesquelético/patología , Sistema Musculoesquelético/fisiopatología , Miocardio/patología , Obesidad/complicaciones , Obesidad/fisiopatología , Ratas , Ratas Sprague-Dawley , Ultrasonografía , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/etiología , Enfermedades Vasculares/patología , Enfermedades Vasculares/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/patología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
The novel SARS-CoV-2 coronavirus is responsible for the infectious disease caused by coronavirus 19 (COVID-19). The current pandemic is growing worldwide and could affect 50-60% of the world population in the months to come. The most severe disease manifestations are atypical pneumonia and sepsis, but the gastrointestinal tract, particularly the liver, has recently been reported to be affected by SARS-CoV-2. Therefore, the aim of the present work was to review the literature available on the topic and provide information about COVID-19, in both healthy and diseased livers, and issue recommendations. The incidence of liver injury specifically associated with COVID-19 varies from 14.8-53%. The majority of case series have reported altered ALT and AST, elevated total bilirubin, and low serum albumin and liver compromise has been associated with the most severe cases of COVID-19. Cirrhosis of the liver has a recognized immune dysfunction status that includes immunodeficiency and systemic inflammation, making it reasonable for those patients to be more susceptible to SARS-CoV-2 infection. The recommendations for those patients, in addition to the general measures of physical distancing and handwashing for all persons, include social, medical, and psychologic support during the period of home quarantine to prevent lapses in treatment. Patients should be made aware that they need to keep abreast of changes in recommendations and social policies.
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Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/fisiopatología , Cirrosis Hepática/terapia , Hepatopatías/etiología , Hepatopatías/fisiopatología , Hígado/fisiopatología , Neumonía Viral/complicaciones , Neumonía Viral/fisiopatología , COVID-19 , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/terapia , Humanos , Incidencia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Cirrosis Hepática/fisiopatología , Hepatopatías/terapia , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/terapiaRESUMEN
The objective of this study was to determine the effects of cadmium (Cd) on histological changes, lipid metabolism, and oxidative and endoplasmic reticulum (ER) stress in the liver of layers. A total of 480 hens at 38 wk of age were randomly assigned in 5 groups that were fed a basal diet or basal diet supplemented with CdCl2 2.5H2O at 7.5, 15, 30, and 60 mg Cd/kg feed for 9 wk. The results showed that accumulation of Cd was the greatest in the kidney, followed by the liver, pancreas, and lung. Diet contaminated with 30 mg Cd/kg induced antioxidant defenses accompanied by the increase of the activities of antioxidant enzymes in the liver, while dietary supplementation with 60 mg Cd/kg decreased the antioxidant levels significantly (P < 0.05). Immunofluorescence assay showed Cd induced reactive oxygen species production and endoplasmic reticulum stress in hepatocytes. Exposure to 60 mg Cd/kg significantly upregulated the expression of cytochrome C, caspase 3, caspase 9, caspase 7, Grp78, and Chop (P < 0.05). Histopathology and quantitative real-time PCR results presented periportal fibrosis, bile duct hyperplasia, and periportal inflammatory cell infiltration in the liver accompanied by upregulating the expression of tumor necrosis factor-α, IL-6 and IL-10 in the 30- or 60-mg Cd/kg groups. Oil Red O staining and RT-qPCR results showed dietary supplementation with 7.5, 15, and 30 mg Cd/kg promoted the synthesis of lipid droplets and upregulated the expression of fatty acid synthase, while dietary supplementation with 60 mg Cd/kg attenuated the synthesis of lipid droplets and downregulated the expression of acyl-CoA oxidase 1, carnitine palmitoyltransferase-1, and perixisome proliferation-activated receptor α (P < 0.05). Besides, the expression of vitellogenin (VTG) II and microsomal triglyceride transfer protein were upregulated in the 7.5-mg Cd/kg group, and the expressions of apolipoprotein B, vitellogenin II, and apolipoprotein very-low-density lipoprotein-II were downregulated in the 30- and/or 60-mg Cd/kg groups (P < 0.05). Conclusively, although low-dose Cd exposure promoted the synthesis of lipids and lipoproteins in the liver, the increase of Cd exposure could trigger liver injury through inducing oxidative and endoplasmic reticulum stress and negatively affect lipid metabolism and yolk formation in laying hens.