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ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic liver diseases (CLD) are liver disorders resulting from abnormal bile formation, secretion, and excretion from various causes. Due to the lack of suitable and safe medications, liver transplantation is the ultimate treatment for CLD patients. Isoastragaloside I (IAS I) is one of the main saponin found in Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge, which has been demonstrated to obviously alleviate CLD. Nevertheless, the IAS I's specific anti-CLD mechanism remains undecipherable. AIM OF THE STUDY: This study's purpose was to elucidate the protective consequence of IAS I on 0.1% 3, 5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC) diet-induced CLD mice, and to reveal its potential mechanism. MATERIALS AND METHODS: In this study, mice with CLD that had been fed a 0.1% DDC diet were distributed two doses of IAS I (20 mg/kg, 50 mg/kg). The effects of IAS I on CLD models were investigated by assessing blood biochemistry, liver histology, and Hyp concentrations. We investigated markers of liver fibrosis and ductular reaction using immunohistochemistry, Western blot, and qRT-PCR. Liver inflammation indicators, arachidonic acid (ARA), and ω-3 fatty acid (FA) metabolites were also analyzed. Quantitative determination of 39 bile acids (BAs) in different organs employing UHPLC-Q-Exactive Orbitrap HRMS technology. Additionally, the H&E and Western blot analysis were used to evaluate differences in intestinal barrier function in DDC-induced mice before and after administering IAS I. RESULTS: After treatment with IAS I, serum biochemical indicators and liver hydroxyproline (Hyp) increased in a dose-dependent manner in CLD mice. The IAS I group showed significant improvement in indicators of liver fibrosis and ductular response, including as α-smooth muscle actin (α-SMA) and cytokeratin 19 (CK19), and transforming growth factor-ß (TGF-ß)/Smads signaling pathway. And inflammatory factors: F4/80, tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), ARA and ω-3 FA metabolites showed significant improvement following IAS I treatment. Moreover, IAS I significantly ameliorated liver tau-BAs levels, particularly TCA, THCA, THDCA, TCDCA, and TDCA contents, which were associated with enhanced expression of hepatic farnesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (Cyp7a1), and bile-salt export pump (BSEP). Furthermore, IAS I significantly improved pathological changes and protein expression related to intestinal barrier function, including zonula occludens protein 1 (ZO-1), Muc2, and Occludin. CONCLUSIONS: IAS I alleviated cholestatic liver injury, relieved inflammation, improved the altered tau-BAs metabolism and restored intestinal barrier function to protect against DDC-induced cholestatic liver diseases.
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Ácidos y Sales Biliares , Colestasis , Saponinas , Animales , Ácidos y Sales Biliares/metabolismo , Masculino , Ratones , Colestasis/tratamiento farmacológico , Colestasis/metabolismo , Colestasis/patología , Saponinas/farmacología , Saponinas/uso terapéutico , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Ratones Endogámicos C57BL , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismo , Hepatopatías/patología , Hepatopatías/prevención & control , Modelos Animales de Enfermedad , Medicamentos Herbarios ChinosRESUMEN
Liver disease is a global health problem that affects the well-being of tens of thousands of people. Dihydroquercetin (DHQ) is a flavonoid compound derived from various plants. Furthermore, DHQ has shown excellent activity in the prevention and treatment of liver injury, such as the inhibition of hepatocellular carcinoma cell proliferation after administration, the normalization of oxidative indices (like SOD, GSH) in this tissue, and the down-regulation of pro-inflammatory molecules (such as IL-6 and TNF-α). DHQ also exerts its therapeutic effects by affecting molecular pathways such as NF-κB and Nrf2. This paper discusses the latest research progress of DHQ in the treatment of various liver diseases (including viral liver injury, drug liver injury, alcoholic liver injury, non-alcoholic liver injury, fatty liver injury, and immune liver injury). It explores how to optimize the application of DHQ to improve its effectiveness in treating liver diseases, which is valuable for preparing potential therapeutic drugs for human liver diseases in conjunction with DHQ.
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Quercetina , Quercetina/análogos & derivados , Quercetina/farmacología , Quercetina/uso terapéutico , Quercetina/química , Humanos , Animales , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismo , Hepatopatías/prevención & control , Hepatopatías/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/lesiones , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/químicaRESUMEN
Diabetic liver injury (DLI) has raised attention in recent years. Liver injury results from type 2 diabetes mellitus (T2DM), and in turn accelerates T2DM development by exacerbating insulin resistance. However, effective approaches for mitigating DLI are surprisingly rare. Krill oil (KO) is an alternative source of omega-3 polyunsaturated fatty acids, possessing antioxidant and anti-inflammatory capacities. Here we investigated the effect of KO supplementation on DLI in a mouse model of T2DM induced by streptozotocin and high-fat diet. The diabetic mice developed glucose intolerance, elevated serum alanine aminotransferase and aspartate aminotransferase, and hepatic pathological injuries such as vacuolation, lipid accumulation and fibrosis deposition, the effects of which were mitigated by KO. Further investigation showed that KO ameliorated the DM-induced expression of fibrotic and inflammatory genes. Notably, KO dramatically reduced hepatic oxidative gene expression, lipid peroxidation and ROS production, all of which are hallmarks of ferroptosis. The inhibitory effect of KO on ferroptosis was confirmed by the KO-decreased hepatic expression of GPX4, COX2 and ACSL4, as well as the KO-reduced hepatic iron deposition. Further, KO restored hepatic NRF2 antioxidant signaling which combats ferroptosis. The present study may provide KO supplementation as a viable approach for the intervention of DLI.
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Antioxidantes , Diabetes Mellitus Experimental , Euphausiacea , Ferroptosis , Factor 2 Relacionado con NF-E2 , Aceites , Animales , Euphausiacea/química , Antioxidantes/farmacología , Ferroptosis/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Aceites/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/efectos de los fármacos , Ratones , Ácidos Grasos Omega-3/farmacología , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Expresión Génica/efectos de los fármacos , Hepatopatías/etiología , Hepatopatías/prevención & control , Hepatopatías/metabolismo , Hepatopatías/tratamiento farmacológico , Hepatopatías/patologíaRESUMEN
Aim Hepatic ischemia reperfusion injury (HIRI) is a leading cause of mortality post liver transplantation, hypovolemic shock and trauma. In this study, we tested, on molecular bases, the possible protective role of two different derivatives of 2-oxindole in a preclinical model of HIRI in rats. MAIN METHODS: HIRI was operated in male Wistar albino rats and prophylactic treatment with oxindole-curcumin (Coxi) or oxindole-vanillin (Voxi) was carried out before the operation. The biochemical and histopathological investigations, in addition to the mechanistic characterizations of the effect of the tested drugs were performed. KEY FINDINGS: HIRI was assured with elevated liver enzymes and marked changes in histopathological features, inflammatory response and oxidative stress. Pretreatment with Coxi and Voxi improved the hepatic histopathological alterations, reduced the elevated serum liver enzymes level and hepatic Malondialdehyde (MDA) content, increased the hepatic Superoxide Dismutase (SOD) activity and reduced Glutathione (GSH) content, downregulated the expression of TNF-α, IL-6, Nod-Like Receptor p3 (NLRP3), Cleaved caspase1, Cleaved caspase 3 proteins, alongside the expression level of IL-1ß, ICAM-1, VCAM-1 and BAX genes, attenuated NF-кB p-P65 Ser536 and Myeloperoxidase (MPO)-positive neutrophils, and activated the PI3K/AKT pathway. SIGNIFICANCE: Coxi and Voxi have promising hepatoprotective activity against HIRI in rats through ameliorating the biochemical and histopathological alterations, attenuating inflammatory and oxidative stress status by modulating the inflammatory TNF-α/ICAM-1, the pyroptosis NLRP3/Caspase-1, and the antioxidant PI3K/AKT pathways.
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Caspasa 1 , Modelos Animales de Enfermedad , Hígado , Proteína con Dominio Pirina 3 de la Familia NLR , Estrés Oxidativo , Oxindoles , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas Wistar , Daño por Reperfusión , Transducción de Señal , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas , Oxindoles/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Transducción de Señal/efectos de los fármacos , Caspasa 1/metabolismo , Estrés Oxidativo/efectos de los fármacos , Hepatopatías/metabolismo , Hepatopatías/prevención & control , Hepatopatías/patología , Hepatopatías/tratamiento farmacológicoRESUMEN
La enfermedad hepática relacionada con fibrosis quística se observa en el 10% de las personas portadoras de la enfermedad. La terapia con moduladores ha mejorado la morbimortalidad, pero teniendo en cuenta que presentan efectos secundarios infrecuentes es necesario monitorizar. Se analiza el algoritmo propuesto por Eldredge et al, que sugiere las decisiones a tomar basado en el resultado de perfil hepático y su aplicación en la práctica clínica.
Cystic fibrosis-related liver disease is seen in 10% of people with the disease. Therapy with modulators has improved morbidity and mortality, but taking into account that they present infrequent side effects, monitoring is necessary. The algorithm proposed by Eldredge et al is analyzed, which suggests the decisions to be made based on the liver profile result and its application in clinical practice.
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Humanos , Niño , Regulador de Conductancia de Transmembrana de Fibrosis Quística/efectos adversos , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Hepatopatías/etiología , Hepatopatías/prevención & controlRESUMEN
Objective To better understand drivers of disease progression in non-alcoholic steatohepatitis (NASH), we assessed clinical and sociodemographic markers of fibrosis progression in adults with NASH.Patients and methodsPhysician-reported patient demographics and clinical characteristics were utilised from the real-world Global Assessment of the Impact of NASH (GAIN) study. Factors associated with likelihood of fibrosis progression since NASH diagnosis were identified using a logistic regression model.ResultsOverall, 2349 patients in Europe from the GAIN study were included; mean age was 54.6 years and 41% were women. Significant covariates included age, years since diagnosis, employment status, fibrosis stage at diagnosis, type 2 diabetes mellitus, hypertension, liver transplant and liver biopsy at diagnosis. Risk of progression was 1.16 (95% confidence interval 1.121.20; p<0.001) times higher for each additional year since NASH diagnosis and 5.43 (2.6811.37; p<0.001) times higher when physicians proposed a liver transplant at diagnosis. Compared with full-time employed patients, risk of progression was 1.77 (1.192.60; p=0.004) times higher for unemployed patients and 3.16 (1.307.63; p=0.010) times higher for those unable to work due to NASH.ConclusionsDisease duration, NASH severity and presence of other metabolic comorbidities could help to assess risk of progression in patients with NASH. (AU)
Objetivo Para comprender mejor los factores que impulsan la progresión de la enfermedad en la esteatohepatitis no alcohólica (NASH), evaluamos los marcadores clínicos y sociodemográficos de la progresión de la fibrosis en adultos con NASH.Pacientes y métodosSe utilizaron las características demográficas y clínicas de los pacientes informadas por los médicos del estudio de Evaluación Global del Impacto de NASH (GAIN) del mundo real. Los factores asociados con la probabilidad de progresión de la fibrosis desde el diagnóstico de EHNA se identificaron mediante un modelo de regresión logística.ResultadosEn total, se incluyeron 2.349 pacientes en Europa del estudio GAIN; la edad media fue 54,6 años y el 41% eran mujeres. Las covariables significativas incluyeron edad, años desde el diagnóstico, situación laboral, estadio de fibrosis en el momento del diagnóstico, diabetes mellitus tipo 2, hipertensión, trasplante de hígado y biopsia de hígado en el momento del diagnóstico. El riesgo de progresión fue 1,16 (intervalo de confianza del 95% 1,12-1,20; p < 0,001) veces mayor por cada año adicional desde el diagnóstico de EHNA y 5,43 (2,68-11,37; p < 0,001) veces mayor cuando los médicos propusieron un trasplante de hígado. en el momento del diagnóstico. En comparación con los pacientes empleados a tiempo completo, el riesgo de progresión fue 1,77 (1,19-2,60; p = 0,004) veces mayor para los pacientes desempleados y 3,16 (1,30-7,63; p = 0,010) veces mayor para aquellos que no podían trabajar debido a a NASH.ConclusionesLa duración de la enfermedad, la gravedad de NASH y la presencia de otras comorbilidades metabólicas podrían ayudar a evaluar el riesgo de progresión en pacientes con NASH. (AU)
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Hepatopatías/prevención & control , Cirrosis Hepática/prevención & control , Cirrosis Hepática/terapia , Biopsia , Factores de RiesgoRESUMEN
Limosilactobacillus reuteri (L. reuteri) is an efficacious probiotic that could reduce inflammation and prevent metabolic disorders. Here, we innovatively found that Polygonatum kingianum polysaccharides (PKP) promoted proliferation and increased stability of L. reuteri WX-94 (a probiotic strain showing anti-inflammation potentials) in simulated digestive fluids in vitro. PKP was composed of galactose, glucose, mannose, and arabinose. The cell-free supernatant extracted from L. reuteri cultured with PKP increased ABTSâ¢+, DPPHâ¢, and FRAP scavenging capacities compared with the supernatant of the medium without PKP and increased metabolites with health-promoting activities, e.g., 3-phenyllactic acid, indole-3-lactic acid, indole-3-carbinol, and propionic acid. Moreover, PKP enhanced alleviating effects of heat-inactivated L. reuteri on high-fat-high-sucrose-induced liver injury in rats via reducing inflammation and regulating expressions of protein and genes involved in fatty acid metabolism (such as HIF1-α, FAßO, CPT1, and AMPK) and fatty acid profiles in liver. Such benefits correlated with its prominent effects on enriching Lactobacillus and short-chain fatty acids while reducing Dubosiella, Fusicatenilacter, Helicobacter, and Oscillospira. Our work provides novel insights into the probiotic property of PKP and emphasizes the great potential of the inactivated L. reuteri cultured with PKP in contracting unhealthy diet-induced liver dysfunctions and gut dysbacteriosis.
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Disbiosis , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Polisacáridos , Probióticos , Animales , Limosilactobacillus reuteri/metabolismo , Probióticos/administración & dosificación , Ratas , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/administración & dosificación , Polisacáridos/metabolismo , Humanos , Disbiosis/microbiología , Disbiosis/prevención & control , Ratas Sprague-Dawley , Hígado/metabolismo , Dieta Alta en Grasa/efectos adversos , Calor , Hepatopatías/prevención & control , Hepatopatías/etiología , Hepatopatías/metabolismo , Hepatopatías/microbiologíaRESUMEN
Sepsis frequently causes systemic inflammatory response syndrome and multiple organ failure in patients. Neoastilbin (NAS) is a flavonoid that plays vital functions in inflammation. This work aims to investigate the protective effects of NAS against sepsis-induced liver and kidney injury and elucidate its underlying mechanisms. The mouse model was established using cecal ligation puncture (CLP) induction. NAS was given to mice by gavage for 7 consecutive days before surgery. Liver and kidney function, oxidative stress, and inflammatory factors in serum or tissues were examined by ELISA or related kits. The expression of relevant proteins was assessed by Western blot. Hematoxylin and eosin and/or periodic acid-Schiff staining revealed that NAS ameliorated the pathological damage in liver and kidney tissues of CLP-induced mice. NAS improved liver and kidney functions, as evidenced by elevated levels of blood urea nitrogen, Creatinine, ALT, and AST in the serum of septic mice. TUNEL assay and the expression of Bcl-2 and Bax showed that NAS dramatically reduced apoptosis in liver and renal tissues. NAS treatment lowered the levels of myeloperoxidase and malondialdehyde, while elevated the superoxide dismutase content in liver and kidney tissues of CLP-induced mice. The levels of inflammatory cytokines (IL-6, TNF-α, and IL-1ß) in the serum and both tissues of CLP-injured mice were markedly decreased by NAS. Mechanically, NAS downregulated TLR4 expression and inhibited NF-κB activation, and overexpression of TLR4 reversed the protective effects of NAS against liver and kidney injury. Collectively, NAS attenuated CLP-induced apoptosis, oxidative stress, inflammation, and dysfunction in the liver and kidney by restraining the TLR4/NF-κB pathway.
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FN-kappa B , Estrés Oxidativo , Sepsis , Transducción de Señal , Receptor Toll-Like 4 , Animales , Receptor Toll-Like 4/metabolismo , FN-kappa B/metabolismo , Sepsis/complicaciones , Sepsis/metabolismo , Sepsis/tratamiento farmacológico , Ratones , Transducción de Señal/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Flavonoles/farmacología , Flavonoles/uso terapéutico , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Modelos Animales de Enfermedad , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/patología , Lesión Renal Aguda/etiología , Apoptosis/efectos de los fármacos , Citocinas/metabolismo , Hepatopatías/etiología , Hepatopatías/prevención & control , Hepatopatías/metabolismo , Hepatopatías/patología , Hepatopatías/tratamiento farmacológico , Ratones Endogámicos C57BLRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng C. A. Meyer) is a precious traditional Chinese medicine with multiple pharmacological effects. Ginsenoside Rg1 is a main active ingredient extracted from ginseng, which is known for its age-delaying and antioxidant effects. Increasing evidence indicates that Rg1 exhibits anti-inflammatory properties in numerous diseases and may ameliorate oxidative damage and inflammation in many chronic liver diseases. AIM OF THE STUDY: Chronic inflammatory injury in liver cells is an important pathological basis of many liver diseases. However, its mechanism remains unclear and therapeutic strategies to prevent its development need to be further explored. Thus, our study is to delve the protective effect and mechanism of Rg1 against chronic hepatic inflammatory injuries induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: The chronic liver damage model in mice was build up by injecting intraperitoneally with LPS (200 µg/kg) for 21 days. Serum liver function indicators and levels of IL-1ß, IL-6 and TNF-α were examined by using corresponding Kits. Hematoxylin and Eosin (H&E), Periodic acid-Schiff (PAS), and Masson stains were utilized to visualize hepatic histopathological damage, glycogen deposition, and liver fibrosis. The nuclear import of p-Nrf2 and the generation of Col4 in the liver were detected by IF, while IHC was employed to detect the expressions of NLRP3 and AIM2 in the hepatic. The Western blot and q-PCR were used to survey the expressions of proteins and mRNAs of fibrosis and apoptosis, and the expressions of Keap1, p-Nrf2 and NLRP3, NLRP1, AIM2 inflammasome-related proteins in mouse liver. The cell viability of human hepatocellular carcinoma cells (HepG2) was detected by Cell Counting Kit-8 to select the action concentration of LPS, and intracellular ROS generation was detected using a kit. The expressions of Nuclear Nrf2, HO-1, NQO1 and NLRP3, NLRP1, and AIM2 inflammasome-related proteins in HepG2 cells were detected by Western blot. Finally, the feasibility of the molecular interlinking between Rg1 and Nrf2 was demonstrated by molecular docking. RESULTS: Rg1 treatment for 21 days decreased the levels of ALT, AST, and inflammatory factors of serum IL-1ß, IL-6 and TNF-α in mice induced by LPS. Pathological results indicated that Rg1 treatment obviously alleviated hepatocellular injury and apoptosis, inflammatory cell infiltration and liver fibrosis in LPS stimulated mice. Rg1 promoted Keap1 degradation and enhanced the expressions of p-Nrf2, HO-1 and decreased the levels of NLRP1, NLRP3, AIM2, cleaved caspase-1, IL-1ß and IL-6 in livers caused by LPS. Furthermore, Rg1 effectively suppressed the rise of ROS in HepG2 cells induced by LPS, whereas inhibition of Nrf2 reversed the role of Rg1 in reducing the production of ROS and NLRP3, NLRP1, and AIM2 expressions in LPS-stimulated HepG2 cells. Finally, the molecular docking illustrated that Rg1 exhibits a strong affinity towards Nrf2. CONCLUSION: The findings indicate that Rg1 significantly ameliorates chronic liver damage and fibrosis induced by LPS. The mechanism may be mediated through promoting the dissociation of Nrf2 from Keap1 and then activating Nrf2 signaling and further inhibiting NLRP3, NLRP1, and AIM2 inflammasomes in liver cells.
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Ginsenósidos , Inflamasomas , Hepatopatías , Humanos , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Lipopolisacáridos/farmacología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Interleucina-6/metabolismo , Simulación del Acoplamiento Molecular , Hígado , Hepatocitos/metabolismo , Hepatopatías/tratamiento farmacológico , Hepatopatías/prevención & control , Hepatopatías/metabolismo , Cirrosis Hepática/metabolismo , FibrosisRESUMEN
Chronic liver disease is a significant global health problem. Epidemiological trends do not show improvement in chronic liver disease incidence but rather a shift in etiologies, with steatotic liver disease (SLD) from metabolic dysfunction and alcohol becoming increasingly important causes. Consequently, there is a pressing need to develop a comprehensive public health approach for SLD. To that end, we propose a public health framework for preventing and controlling SLD. The framework is anchored on evidence linking physical inactivity, unhealthy dietary patterns, alcohol use, and obesity with both incidence and progression of SLD. Guided by the framework, we review examples of federal/state-level, community-level, and individual-level interventions with the potential to address these determinants of SLD. Ultimately, mitigating SLD's burden requires primary risk factor reduction at multiple socioecological levels, by scaling up the World Health Organization's "best buys," in addition to developing and implementing SLD-specific control interventions.
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Hígado Graso , Hepatopatías , Humanos , Salud Pública , Hepatopatías/epidemiología , Hepatopatías/prevención & control , Factores de Riesgo , Consumo de Bebidas Alcohólicas , Obesidad , Salud GlobalRESUMEN
One of the principles of prevention and non-medicamentous treatment of liver diseases, including hepatitis of different etiology, is the normalization of the diet through the consumption of food with physiologically active ingredients, in particular betulin, which helps to eliminate the causes of metabolic and oxidative disorders within liver cells. The aim of the research was to assess in vivo the influence of triterpene alcohol betulin extracted from Betula pendula Roth. birch bark in fat-containing products (for example mayonnaise) on the blood biochemical parameters and liver morphological structure of rats with initiated acute toxic hepatitis. Material and methods. Hepatoprotective and antioxidant activities of betulin as part of mayonnaise samples has been investigated in vivo on the model of toxic hepatitis initiated by carbon tetrachloride in male Wistar rats weighing 210-265 g. The animals were divided into 4 groups of 10 animals each: CG-1 - intact, CG-2 and MG - with carbon tetrachloride initiated toxic hepatitis. rats of the main groups were orally administered mayonnaise once a day at a dosage of 1 ml for 21 days after the formation of the model pathology: OG-1 with the added betulin (1 mg per 1 kg of body weight), OG-2 without betulin. Disorders of metabolic and oxidative processes in liver cells of animals were evaluated by biochemical indicators of blood plasma: the level of glucose, albumin, total cholesterol, triglycerides and urea and the activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyltransferase. Oxidative stress in rats was estimated by the activity of catalase and superoxide dismutase in blood hemolysate (at a dilution of 1:200 and 1:10, respectively); the total prooxidant (in blood plasma) and total antioxidant (in blood hemolysate at a dilution of 1:10) activity were determined spectrophotometrically (colored complexes of TWIN-80 oxidation products with thiobarbituric acid). The morphological structure of rats' liver was estimated by microscopy of prepared cuts of hepatic tissue. Results. Based on biochemical parameters of rat blood plasma, it has been established that the administration of mayonnaise with betulin prevents the development of cytolic syndrome and suppresses the process of peroxidation by directly neutralizing free radicals. Aspartate aminotransferase and alkaline phosphatase activity in blood plasma of the experimental animals of the main group MG-1 reduced by 20.7 and 35.2% compared with indicators of the rats of the main group MG-2. Glucose concentration normalized to the level of the control group CG-1. The concentration of bilirubin and triglycerides decreased by 22.9 and by 48.1%, which indicates a significant reduction in the indicators of cholestatic syndrome in the group of animals OG-1 compared to OG-2. The total prooxidant activity and the concentration of thiobarbiturate-reactive products decreased compared to the CG-2 and MG-2 groups, which indicates the suppression of oxidative stress and, as a result, an improvement in liver conditions of animals with toxic hepatitis even when taking a fat-containing product. In liver histopeparates of animals receiving mayonnaise with betulin, necrobotic changes were less pronounced in comparison with the group MG-2. They were estimated at 1 point: small-drip dystrophy spots were found, haemorrhages in the interregional septum with inflammatory infiltration in the course of hemorrhages against the presence of necrosis hepatocytes with pronounced adipose dystrophy in the centres of the lobules, step necrosis with signs of replacing the damaged hepatocytes of the connective tissue, accompanied by centrolobular hemorrhages in MG-2 rats. Conclusion. Introduced into the composition of mayonnaise betulin, reduces the development of cytolic syndrome in toxic hepatitis and suppresses the process of peroxidation, on the basis of which fat-containing foods with betulin can be recommended for clinical examination as specialized products in acute and chronic liver diseases, including complicated cholestasis.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatopatías , Triterpenos , Ratas , Masculino , Animales , Antioxidantes/metabolismo , Ratas Wistar , Tetracloruro de Carbono/metabolismo , Tetracloruro de Carbono/farmacología , Triterpenos/farmacología , Triterpenos/metabolismo , Fosfatasa Alcalina , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismo , Hepatopatías/prevención & control , Hígado/metabolismo , Estrés Oxidativo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Animales de Laboratorio/metabolismo , Necrosis/tratamiento farmacológico , Necrosis/metabolismo , Triglicéridos/metabolismo , Hemorragia/tratamiento farmacológico , Hemorragia/metabolismo , Glucosa/metabolismo , Glucosa/farmacología , Peroxidación de LípidoRESUMEN
BACKGROUND/AIMS: The major complication of liver resection is hepatic ischemia/reperfusion injury. Propofol appears to have organprotective effects. Our study aimed to study the protective role of propofol against hepatic ischemia/reperfusion injury and the potential mechanisms. MATERIALS AND METHODS: Mice and human hepatocytes (LO2) were used to establish 2 models: the ischemia/reperfusion injury model in vivo and the hypoxia/reoxygenation model in vitro, respectively. Alanine and aspartate aminotransferase serum levels were detected to evaluate the extent of hepatic cellular injury. Malondialdehyde, superoxide dismutase, glutathione, and catalase expression levels were measured to evaluate the oxidative damage in mice liver. Lactate dehydrogenase levels were detected for hepatocyte cytotoxicity severity. Nuclear factor, erythroid-like 2 and heme oxygenase 1 expression levels were detected. RESULTS: In the ischemia/reperfusion model, propofol pretreatment significantly reduced the alanine aminotransferase and aspartate aminotransferase expression levels, alleviating the hepatic cellular injury. Propofol also protected the mice liver from oxidative damage. In the hypoxia/reoxygenation model, propofol pretreatment reduced lactate dehydrogenase expression levels, suggesting its protective effects in LO2 cells. Furthermore, propofol increased the nuclear factor, erythroid-like 2 and heme oxygenase 1 expression levels both in vivo and in vitro. CONCLUSION: Propofol acts through the nuclear factor, erythroid-like 2, and heme oxygenase 1 pathway to protect the mice liver against ischemia/reperfusion injury and hepatocytes against hypoxia/reoxygenation injury. Propofol should be used as an effective therapeutic drug for hepatic ischemia/reperfusion injury.
Asunto(s)
Hepatopatías , Propofol , Daño por Reperfusión , Humanos , Ratones , Animales , Propofol/farmacología , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/farmacología , Hemo-Oxigenasa 1/uso terapéutico , Hepatocitos/metabolismo , Hepatopatías/etiología , Hepatopatías/prevención & control , Hepatopatías/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/tratamiento farmacológico , Isquemia/metabolismo , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Aspartato Aminotransferasas , Lactato Deshidrogenasas/metabolismoRESUMEN
Exhaustive exercise (EE) induces liver injury and has recently gained much attention. Sulforaphane (SFN) can protect the liver from inflammation and oxidative stress. However, the effects of SFN on EE-induced liver injury and its underlying mechanisms are still unclear. C57BL/6J mice swimming to exhaustion for seven days were used to simulate the liver injury caused by EE. Different doses of SFN (10, 30, 90 mg/kg body weight) were gavage-fed one week before and during the exercise. SFN intervention significantly reduced the EE-induced lactate dehydrogenase (LDH), creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum, as well as attenuating liver tissue morphological abnormality, oxidative stress injury, and inflammation. Liver transcriptomic analysis showed that the differentially expressed genes altered by SFN intervention in the exercise model were mainly enriched in glucose and lipid metabolism pathways. The most altered gene by SFN intervention screened by RNA-seq and validated by qRT-PCR is Ppp1r3g, a gene involved in regulating hepatic glycogenesis, which may play a vital role in the protective effects of SFN in EE-induced liver damage. SFN can protect the liver from EE-induced damage, and glucose and lipid metabolism may be involved in the mechanism of the protective effects.
Asunto(s)
Ejercicio Físico , Isotiocianatos , Hepatopatías , Hígado , Sulfóxidos , Hígado/lesiones , Sulfóxidos/farmacología , Isotiocianatos/farmacología , Estrés Oxidativo , Transcriptoma , Animales , Ratones , Hepatopatías/metabolismo , Hepatopatías/prevención & control , Ratones Endogámicos C57BL , Glucosa/metabolismo , LípidosRESUMEN
BACKGROUND & AIMS: At least 20%-30% of patients with intestinal failure receiving long-term parenteral nutrition will develop intestinal failure-associated liver disease (IFALD), for which there are few therapeutic options. SEFA-6179 is a first-in-class structurally engineered medium-chain fatty acid analogue that acts through GPR84, PPARα, and PPARγ agonism. We hypothesized that SEFA-6179 would prevent biochemical and histologic liver injury in a preterm piglet model of IFALD. METHODS: Preterm Yorkshire piglets were delivered by cesarean section, and parenteral nutrition was provided for 14 days via implanted central venous catheters. Animals were treated with either medium-chain triglyceride vehicle control or SEFA-6179. RESULTS: Compared to medium-chain triglyceride vehicle at day of life 15, SEFA-6179 prevented biochemical cholestasis (direct bilirubin: 1.9 vs <0.2 mg/dL, P = .01; total bilirubin: 2.7 vs 0.4 mg/dL, P = .02; gamma glutamyl transferase: 172 vs 30 U/L, P = .01). SEFA-6179 also prevented steatosis (45.6 vs 13.9 mg triglycerides/g liver tissue, P = .009), reduced bile duct proliferation (1.6% vs 0.5% area cytokeratin 7 positive, P = .009), and reduced fibrosis assessed by a masked pathologist (median Ishak score: 3 vs 1, P = 0.007). RNA sequencing of liver tissue demonstrated that SEFA-6179 broadly impacted inflammatory, metabolic, and fibrotic pathways, consistent with its in vitro receptor activity (GPR84/PPARα/PPARγ agonist). CONCLUSIONS: In a preterm piglet model of IFALD, SEFA-6179 treatment prevented biochemical cholestasis and steatosis and reduced bile duct proliferation and fibrosis. SEFA-6179 is a promising first-in-class therapy for the prevention and treatment of IFALD that will be investigated in an upcoming phase II clinical trial.
Asunto(s)
Colestasis , Enfermedades Intestinales , Insuficiencia Intestinal , Hepatopatías , Fallo Hepático , Embarazo , Animales , Femenino , Porcinos , Cesárea , PPAR alfa/metabolismo , PPAR gamma/metabolismo , Hígado/metabolismo , Hepatopatías/prevención & control , Hepatopatías/complicaciones , Enfermedades Intestinales/prevención & control , Enfermedades Intestinales/complicaciones , Colestasis/metabolismo , Bilirrubina , Ácidos Grasos/metabolismo , Fibrosis , Triglicéridos/metabolismoRESUMEN
Background: Cholestasis is a health problem, both in humans and animals, which in the disease's course involves oxidative stress, inflammation, and liver fibrosis. EA has been proven to have beneficial effects on various diseases. Aim: This study was conducted to determine the effect of EA in protecting liver damage because of cholestasis. In addition, to understand the underlying mechanism of liver damage in rats as a model animal by bile duct ligation (BDL) technique. Methods: In this study, male adult rats were used and randomly divided into three treatment groups. S is the sham-operated group, BDL is the group that is treated with BDL and the BDL-EA group is treated with BDL and given EA by gavage at a dose of 60 mg/kg bw/day, starting on the second day after BDL and given for 21 days. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT) were evaluated using spectrophotometer; tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-ß1) were evaluated using sandwich ELISA and histopathological examination using HE and Massion's Trichrome staining. Results: In this study, BDL significantly increased serum levels of AST, ALT, ALP, and hepatic GGT. In addition, BDL also increased levels of TNF-α, and TGF-ß1 compared to sham-operated controls. Histological studies in the BDL group also showed that the BDL increased the degree of necro-inflammation and collagen deposition area in the liver compared to the sham-operated group. Administration of EA has been shown to significantly improve liver morpho-function of the liver. I attenuated these changes in the BDL-EA group, where all observed study variables appeared to have improved. Conclusion: EA has been shown to reduce cholestasis that causes liver injury and improves liver enzyme profiles, and is suspected to have occurred because of its activities as an antioxidant, anti-inflammatory, and anti-fibrotic.
Asunto(s)
Colestasis , Hepatopatías , Granada (Fruta) , Animales , Masculino , Ratas , Colestasis/complicaciones , Colestasis/tratamiento farmacológico , Colestasis/metabolismo , Colestasis/veterinaria , Ácido Elágico/farmacología , Ácido Elágico/uso terapéutico , Frutas/metabolismo , Inflamación/veterinaria , Hepatopatías/tratamiento farmacológico , Hepatopatías/etiología , Hepatopatías/prevención & control , Hepatopatías/veterinaria , Factor de Crecimiento Transformador beta1/uso terapéutico , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
Liver problems are a worldwide concern, and conventional medicinal therapies are ineffective. Hence, safeguarding the healthy liver is vital for good health and well-being. Infections due to virus, immune problems, cancer, alcohol abuse, and an overdose of drugs are some of the causes of liver diseases. Antioxidants derived from medicinal plants and conventional dietary sources can protect the liver from damages caused by oxidative stress system and various chemicals. Plants and plant-derived phytochemicals are appealing hepatoprotective agents since they have less side effects and still there is a lot of interest shown in using herbal tonics for treating liver disorders. This review therefore primarily focuses on newly discovered medicinal plants and compounds produced from plants that fall under the classifications of flavonoids, alkaloids, terpenoids, polyphenolics, sterols, anthocyanins, and saponin glycosides, all of which have the potential to be hepatoprotective. Hosta plantaginea, Ligusticum chuanxiong, Daniella oliveri, Garcinia mangostana, Solanum melongena, Vaccinium myrtillus, Picrorhiza kurroa, and Citrus medica are some potential plants having hepatoprotective effects. We conclude that these phytochemicals and the plant extracts listed above are used in the future to treat a variety of liver diseases, additional research is still needed to develop safer and more potent phytochemical drugs.
Asunto(s)
Hepatopatías , Plantas Medicinales , Plantas Medicinales/química , Fitoterapia , Antocianinas/uso terapéutico , Hepatopatías/tratamiento farmacológico , Hepatopatías/prevención & control , Fitoquímicos/farmacología , Fitoquímicos/uso terapéuticoRESUMEN
BACKGROUND: Intestinal failure-associated liver disease (IFALD) occurs in up to 50% of neonates treated with prolonged parenteral nutrition. Preventative strategies for IFALD include soybean oil lipid emulsion (SOLE) minimization and use of mixed-oil intravenous lipid emulsions (ILE). We conducted a pilot study prospectively comparing these two ILE strategies in the prevention of IFALD in neonates who required abdominal surgery. METHODS: We randomized eligible neonates to SOLE at 1 g/kg/day (SOLE Min) or mixed-oil ILE containing fish oil (MOLE) at 3 g/kg/day. These treatment groups were also compared with historic controls who received SOLE at 2-3 g/kg/day (SOLE Historic). We defined IFALD as a direct bilirubin >2 mg/dl on two measurements. Secondary outcomes included laboratory, growth, clinical, and nutrition outcomes. RESULTS: A total of 24 prospective and 24 historic patients were included. There was no difference in the rate of IFALD. However, there was a difference in the weekly change of direct bilirubin levels (SOLE Historic +0.293 mg/dl/week vs MOLE, P < 0.001; SOLE Min +0.242 mg/dl/week vs MOLE, P < 0.001). The MOLE group also had a lower direct bilirubin at study completion (SOLE Historic, 1.7 ± 1.7 mg/dl; SOLE Min, 1.6 ± 1.4 mg/dl; MOLE, 0.4 ± 0.4 mg/dl; P = 0.002) and received greater total calories (P = 0.008). CONCLUSION: The rate of IFALD did not differ when comparing ILE strategies in neonates requiring abdominal surgery. However, the MOLE group maintained significantly lower direct bilirubin levels over time while receiving increased calories. This pilot study highlights the need for further randomized controlled trials comparing these ILE strategies.