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1.
Lancet ; 395(10219): 226-239, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31791690

RESUMO

This final report of the Lancet Commission into liver disease in the UK stresses the continuing increase in burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions which are worsening in deprived areas. Only with comprehensive food and alcohol strategies based on fiscal and regulatory measures (including a minimum unit price for alcohol, the alcohol duty escalator, and an extension of the sugar levy on food content) can the disease burden be curtailed. Following introduction of minimum unit pricing in Scotland, alcohol sales fell by 3%, with the greatest effect on heavy drinkers of low-cost alcohol products. We also discuss the major contribution of obesity and alcohol to the ten most common cancers as well as measures outlined by the departing Chief Medical Officer to combat rising levels of obesity-the highest of any country in the west. Mortality of severely ill patients with liver disease in district general hospitals is unacceptably high, indicating the need to develop a masterplan for improving hospital care. We propose a plan based around specialist hospital centres that are linked to district general hospitals by operational delivery networks. This plan has received strong backing from the British Association for Study of the Liver and British Society of Gastroenterology, but is held up at NHS England. The value of so-called day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and, in particular, schemes to allow general practitioners to refer patients directly for elastography assessment. New funding arrangements for general practitioners will be required if these proposals are to be taken up more widely around the country. Understanding of the harm to health from lifestyle causes among the general population is low, with a poor knowledge of alcohol consumption and dietary guidelines. The Lancet Commission has serious doubts about whether the initiatives described in the Prevention Green Paper, with the onus placed on the individual based on the use of information technology and the latest in behavioural science, will be effective. We call for greater coordination between official and non-official bodies that have highlighted the unacceptable disease burden from liver disease in England in order to present a single, strong voice to the higher echelons of government.


Assuntos
Alcoolismo/epidemiologia , Hepatopatias/epidemiologia , Hepatopatias/prevenção & controle , Obesidade/epidemiologia , Bebidas Alcoólicas/economia , Alcoolismo/complicações , Alcoolismo/terapia , Comércio , Redes Comunitárias/organização & administração , Comorbidade , Efeitos Psicossociais da Doença , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Legislação sobre Alimentos , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Transplante de Fígado/estatística & dados numéricos , Obesidade/complicações , Pacotes de Assistência ao Paciente , Escócia , Reino Unido/epidemiologia
2.
J Stroke Cerebrovasc Dis ; 29(2): 104562, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31836361

RESUMO

INTRODUCTION: Recent studies have indicated that the damaging effects of stroke are not only limited to the brain. We sought to examine the changes of liver and renal enzymes in the acute phase of ischemic stroke and to investigate possible explanations and therapeutic options, concerning in particular the functional alterations of peripheral organs after administration of an anti-inflammatory agent. MATERIAL/METHODS: Twelve-week-old Wistar male rats were randomly divided into control and Cyclosporine groups (n = 10 each). Cyclosporine was given orally by gavage for 5 days prior to cerebral ischemia at a total volume of 15 mg/kg/day. All animals were subjected to 60 minutes focal ischemia by filament occlusion of the middle cerebral artery. Serum concentrations of Creatinine, Urea, SGOT, SGPT, and γGT were determined at the time before surgery and after 60 minutes brain ischemia. RESULTS: Comparing data of 2 time-points, in both groups the serum liver enzyme levels increased progressively during the ischemic period. The liver enzymes and Urea were significantly lower in the Cyclosporine group than in the control group and the levels of Creatinine were slightly higher in the Cyclosporine group, in both time-points. CONCLUSIONS: The detection of high liver enzyme serum levels in the acute phase of ischemic stroke implies the secondary effect of cerebral infraction on the peripheral organs and particularly on the liver function. Cyclosporine seems to exhibit a protective activity and to affect both liver and renal function after ischemic stroke.


Assuntos
Anti-Inflamatórios/farmacologia , Isquemia Encefálica/tratamento farmacológico , Ciclosporina/farmacologia , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Rim/enzimologia , Rim/fisiopatologia , Nefropatias/sangue , Nefropatias/etiologia , Nefropatias/fisiopatologia , Fígado/enzimologia , Fígado/fisiopatologia , Hepatopatias/sangue , Hepatopatias/etiologia , Hepatopatias/fisiopatologia , Masculino , Ratos Wistar , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo
3.
J Agric Food Chem ; 67(50): 13948-13959, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31698901

RESUMO

The aim of this study was to investigate the protective effect of punicalagin (PU), which is a main component of pomegranate polyphenols, against liver injury induced by Type 2 diabetes mellitus (T2DM) and to explore the molecular mechanism based on autophagy in vivo and in vitro. In T2DM mice, we found that PU significantly improved liver histology, reversed serum biochemical abnormalities, and increased the autophagosome number in the liver. In HepG2 cells cultured in a high-glucose environment, PU upregulated the glucose uptake level. Both in vivo and in vitro, PU upregulated the expression of autophagy-related proteins, such as LC3b and p62, and reduced the phosphorylated Akt/total Akt and phosphorylated FoxO3a/total FoxO3a protein ratios, and these effects were enhanced by LY294002 (a PI3K/Akt inhibitor). In summary, our current findings suggest that PU protects against liver injury induced by T2DM by restoring autophagy through the Akt/FoxO3a signaling pathway.


Assuntos
Autofagia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Proteína Forkhead Box O3/metabolismo , Taninos Hidrolisáveis/administração & dosagem , Hepatopatias/prevenção & controle , Fígado/lesões , Substâncias Protetoras/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Proteína Forkhead Box O3/genética , Humanos , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos
4.
Acta Cir Bras ; 34(7): e201900707, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31531528

RESUMO

PURPOSE: To evaluate the effects of splenic ischemic preconditioning (sIPC) on oxidative stress induced by hepatic ischemia-reperfusion in rats. METHODS: Fifteen male Wistar rats were equally divided into 3 groups: SHAM, IRI and sIPC. Animals from IRI group were subjected to 45 minutes of partial liver ischemia (70%). In the sIPC group, splenic artery was clamped in 2 cycles of 5 min of ischemia and 5 min of reperfusion (20 min total) prior to hepatic ischemia. SHAM group underwent the same surgical procedures as in the remaining groups, but no liver ischemia or sIPC were induced. After 1h, hepatic and splenic tissue samples were harvested for TBARS, CAT, GPx and GSH-Rd measurement. RESULTS: sIPC treatment significantly decreased both hepatic and splenic levels of TBARS when compared to IRI group (p<0.01). Furthermore, the hepatic and splenic activities of CAT, GPx and GSH- Rd were significantly higher in sIPC group than in IRI group. CONCLUSION: sIPC was able to attenuate hepatic and splenic IRI-induced oxidative stress.


Assuntos
Precondicionamento Isquêmico/métodos , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Estresse Oxidativo/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Fígado/fisiologia , Hepatopatias/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia
5.
Medicina (Kaunas) ; 55(9)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505863

RESUMO

Background and Objectives: Dyslipidemia is gaining much attention among healthcare professionals because of its high association with the malfunctioning of a number of normal physiological and metabolic processes in the body. Obesity is directly interconnected with dyslipidemia and is said to be a denouement of hyperlipidemia and, if left untreated, may lead to intense damage to organs that are directly involved in fat metabolism. The objective of this study was to investigate the synergistic antiobesity and anti-hyperlipidemic activities along with hepato- and renoprotective potential of nanoemulsomes (NES) of lovastatin (LTN)-loaded ginger (GR) and garlic (GL) oils. Materials and Methods: LTN nanoemulsomes co-encapsulated with GR oil and GL oil were prepared by a thin hydration technique. Eight-week-old male Wistar rats weighing 200-250 g were induced with hyperlipidemia via a high-fat diet (HFD) comprising 40% beef tallow. Body weight, serum biochemical lipid parameters, and those for liver and kidney functions, serum TC, LDL-C, vLDL-C, HDL-C, TG, atherogenic index (AI), ALT, AFT, ALP, γ-GT, total protein (TP), serum albumin and globulin ratio (A/G), serum creatinine, blood urea nitrogen (BUN) and blood urea, and histopathology of hematoxylin and eosin (H&E) stained liver and kidney sections of all aforementioned groups were examined in the treated animals. Results: Nanoemulsomes of LTN-loaded GR and GL oils provided synergistic effects with LTN, exerted better ameliorative actions in reducing serum TC, LDL-C, vLDL-C, triglycerides, and AI, and improved serum HDL-C levels. Serum ALT, AST, ALP, and γ-GT levels were in the normal range for nanoemulsome groups. H&E stained liver and kidney sections of these animals confirmed better hepatoprotective and renoprotective effects than LTN alone. Serum biochemical parameters for renal functions also claimed to be in the moderate range for nanoemulsome-treated groups. Conclusion: This study demonstrated that nanoemulsomes of LTN-loaded GR and GL oils synergistically provided better antihyperlipidemic, hepatoprotective, and renoprotective effects as compared to LTN alone.


Assuntos
Fármacos Antiobesidade/farmacologia , Alho , Gengibre , Hipolipemiantes/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Lovastatina/farmacologia , Óleos Vegetais , Administração Oral , Animais , Fármacos Antiobesidade/administração & dosagem , Emulsões , Hiperlipidemias/complicações , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Nefropatias/etiologia , Nefropatias/prevenção & controle , Hepatopatias/etiologia , Hepatopatias/prevenção & controle , Lovastatina/administração & dosagem , Masculino , Nanoestruturas , Ratos , Ratos Wistar
6.
Transplant Proc ; 51(8): 2828-2832, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493917

RESUMO

OBJECTIVE: Hepatic ischemia and reperfusion (I/R) is a destructive event associated with high rates of liver failure after liver transplantation. Hesperidin significantly contributes to the antioxidant defense system and has been reported to act as a powerful agent against superoxide and hydroxyl radicals. Our objective was to investigate the protective effect of hesperidin against hepatic IR injury in a rat model. METHODS: We fed Sprague-Dawley rats either hesperidin (100 mg/kg/d) or saline. One week later, ischemia was induced by clamping the rats' common hepatic artery and portal vein for 30 minutes. The rats were divided into 3 groups: 1. the sham operated group; 2. the I/R group; and 3. the I/R-hesperidin group. RESULTS: Compared to the sham group, the I/R group had higher expression of serum aspartate aminotransferase and serum alanine aminotransferase and lower expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, nitric oxide, and albumin. Compared to the I/R group, the I/R-hesperidin group had higher expression of catalase, superoxide dismutase, antioxidant and nitric oxide and lower expression of serum aspartate aminotransferase and serum alanine aminotransferase. CONCLUSIONS: Our findings suggest that hesperidin is a potential therapeutic agent for hepatic I/R injury.


Assuntos
Antioxidantes/uso terapêutico , Hesperidina/uso terapêutico , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Catalase/metabolismo , Modelos Animais de Doenças , Glutationa Peroxidase/metabolismo , Hesperidina/farmacologia , Hepatopatias/metabolismo , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/metabolismo
7.
Transplant Proc ; 51(8): 2823-2827, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493918

RESUMO

OBJECTIVE: Hepatic ischemia reperfusion (I/R) injury is regarded as a serious concern in clinical practice. Citric acid reduces oxidative stress and inflammation during hypoxia and reoxygenation. Our objective was to investigate the protective effect of citric acid against hepatic I/R injury in rats. METHODS: We fed Sprague-Dawley rats either citric acid (100 mg/kg/d) or saline. One week later, ischemia was induced by clamping the rats' common hepatic artery and portal vein for 30 minutes. The rats were randomly divided into 3 major groups that were treated as follows: 1. the sham operated group; 2. the I/R group; and 3. the I/R-citric acid group. RESULTS: Compared to the sham group, the I/R group had higher expression of aspartate aminotransferase and alanine aminotransferase and lower expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, nitric oxide, and albumin. Compared to the I/R group, the I/R-citric acid group had higher expression of catalase, superoxide dismutase, antioxidants, and nitric oxide, and lower expression of aspartate aminotransferase and alanine aminotransferase. CONCLUSIONS: These results suggest that citric acid therapy has significant therapeutic potential in ischemic liver injury.


Assuntos
Antioxidantes/uso terapêutico , Ácido Cítrico/uso terapêutico , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/metabolismo , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Ácido Cítrico/farmacologia , Glutationa Peroxidase/metabolismo , Hepatopatias/metabolismo , Masculino , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/metabolismo
8.
Nat Commun ; 10(1): 4291, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541116

RESUMO

Supplementation with the NAD+ precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously shown that NR kinase 1 (NRK1) is rate-limiting and essential for NR-induced NAD+ synthesis in hepatic cells. To understand the relevance of hepatic NR metabolism, we generated whole body and liver-specific NRK1 knockout mice. Here, we show that NRK1 deficiency leads to decreased gluconeogenic potential and impaired mitochondrial function. Upon high-fat feeding, NRK1 deficient mice develop glucose intolerance, insulin resistance and hepatosteatosis. Furthermore, they are more susceptible to diet-induced liver DNA damage, due to compromised PARP1 activity. Our results demonstrate that endogenous NR metabolism is critical to sustain hepatic NAD+ levels and hinder diet-induced metabolic damage, highlighting the relevance of NRK1 as a therapeutic target for metabolic disorders.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Hepatopatias/prevenção & controle , Niacinamida/análogos & derivados , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Animais , Glicemia , Dano ao DNA , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Predisposição Genética para Doença/genética , Intolerância à Glucose , Hepatócitos/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Fígado/metabolismo , Hepatopatias/genética , Hepatopatias/patologia , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NAD/metabolismo , Niacinamida/genética , Niacinamida/metabolismo , Niacinamida/farmacologia
9.
Medicine (Baltimore) ; 98(31): e16673, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374045

RESUMO

The aim of this study was to analyze dose-volume histogram (DVH) of the remnant liver for postoperative cholangiocarcinoma (CCA) patients, to find toxicity rates, and to confirm efficacy of postoperative radiation therapy (RT).Thirty-two postoperative CCA patients received partial liver resection and postoperative RT with curative intent. The "liver reduction rate" was calculated by contouring liver volume at computed tomography (CT) just before the surgery and at CT for planning the RT. To evaluate late toxicity, the radiation-induced hepatic toxicity (RIHT) was determined by the common terminology criteria for adverse events toxicity grade of bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin, and was defined from 3 months after RT until liver metastasis was revealed. The radiation-induced liver disease (RILD) was also evaluated.Tumor stages were distributed as follows: I: 1, II: 8, IIIA: 1, IIIB: 6, IIIC: 14, IVA: 2. Median prescribed total dose was 50 Gy. Median follow-up time was 27 months. Two-year overall survival (OS): 72.4%, disease-free survival: 47.7%, local control: 65.3%, and the median survival time was 40 months. The median "liver reduction rate" was 21%. The OS had statistically significant difference in nodal status (P = .032) and "liver reduction rate" >30% (P = .016). In the association between the ≥grade 2 RIHT and DVH, there were significantly differences in V30 and V40 (P = .041, P = .034), respectively. The grade ≥2 RIHT rates differ also significantly by sex (P = .008). Two patients (6.2%) were suspected of RILD.We suggest that RT for remnant liver should be considered the liver V30, V40 to prevent radiation-induced liver dysfunction.


Assuntos
Colangiocarcinoma/radioterapia , Hepatopatias/prevenção & controle , Neoplasias Hepáticas/radioterapia , Lesões por Radiação/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Cisplatino/uso terapêutico , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/uso terapêutico , Piridinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Dosagem Radioterapêutica , Radioterapia Adjuvante , Tegafur/uso terapêutico , Tomografia Computadorizada por Raios X
10.
J Med Food ; 22(9): 885-895, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31274380

RESUMO

We have previously demonstrated the hepatoprotective effect of Schisandra chinensis polysaccharides (SCP) against the liver injury induced by alcohol, high-fat diet, and carbon tetrachloride in mice. In this study, we investigated the effect of SCP against the immunological liver injury induced by concanavalin A (Con A) in mice. The results showed that SCP could significantly reduce the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the serum of mice with immunological liver injury. SCP could significantly decrease the content of malondialdehyde (MDA) and nitric oxide (NO) and increase the activity of superoxide dismutase (SOD) and glutathione (GSH) in the liver tissue. SCP could significantly increase the number of CD4+ and decrease the number of CD8+ in the peripheral blood, and elevate the ratio of CD4+/CD8+. SCP could significantly downregulate the expression of Kelch-like ECH-associated protein 1 (Keap1) and upregulate the expression of nuclear factor-erythroid 2-related factor2 (Nrf2) and downstream gene heme oxygenase-1 (HO-1), and downregulate the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), and nuclear factor-kappa B (NF-κB) proteins. This study indicates that SCP can reduce the release of a large number of inflammatory factors to inhibit the oxidative stress in mice with the immunological liver injury induced by Con A, and its mechanism is closely related to the regulation of Nrf2/antioxidant response element and TLR4/NF-κB signaling pathways.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Hepatopatias/prevenção & controle , Fígado/lesões , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Polissacarídeos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Schisandra/química , Receptor 4 Toll-Like/imunologia , Animais , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias/genética , Hepatopatias/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Óxido Nítrico/imunologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
11.
Microb Pathog ; 135: 103637, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31326563

RESUMO

The indiscriminate use of antibiotics is a major concern for the aquaculture industry because of the increasing prevalence of bacterial resistance, including the emergence of multi-resistant strains of Aeromonas hydrophila. Therefore, alternative ecofriendly therapeutic or prophylactic approaches such as natural products have been suggested, including caffeine, a methylxanthine with potent bactericidal and antioxidant properties. The aims of this study were to evaluate whether dietary supplementation with caffeine exerted bactericidal effects against A. hydrophila, and to determine whether caffeine protected the liver of grass carp (Ctenopharyngodon idella) against A. hydrophila-induced oxidative damage. Experiment I evaluated the antimicrobial properties of caffeine dietary supplementation linked to longevity and mortality rates during aeromonosis. Fish infected with A. hydrophila that were fed diets containing 5% and 8% caffeine lived significantly longer than those fed with control diets. Experiment II evaluated hepatic oxidative stress-related parameters and microbial loads on day 7 post-infection. Levels of hepatic reactive oxygen species (ROS), lipid peroxidation (LOOH) and protein carbonylation (PC) levels were significantly higher in infected fish fed with control diet than in uninfected fish, and hepatic antioxidant capacity against peroxyl radicals (ACAP) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) activities were significantly inhibited. Dietary supplementation with 5% and 8% caffeine prevented the increase on hepatic ROS, LOOH and PC levels (except 5% caffeine) elicited by infection. Caffeine supplementation reduced or prevented the inhibition of hepatic SOD, GPx and GST activities. Finally, both caffeine concentrations reduced the hepatic microbial load compared to fish fed with control diets that were infected with A. hydrophila. Taken together, the data suggest that dietary supplementation with 8% caffeine may be considered a compelling prophylactic approach to aeromonosis caused by A. hydrophila.


Assuntos
Carga Bacteriana/efeitos dos fármacos , Cafeína/farmacologia , Suplementos Nutricionais , Doenças dos Peixes/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Hepatopatias/prevenção & controle , Aeromonas hydrophila , Ração Animal , Animais , Antioxidantes/farmacologia , Carpas , Modelos Animais de Doenças , Doenças dos Peixes/microbiologia , Doenças dos Peixes/mortalidade , Proteínas de Peixes , Infecções por Bactérias Gram-Negativas/microbiologia , Peroxidação de Lipídeos , Fígado/lesões , Fígado/patologia , Estresse Oxidativo , Peróxidos , Espécies Reativas de Oxigênio/metabolismo , Taxa de Sobrevida
12.
Gastroenterology ; 157(5): 1368-1382, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31336123

RESUMO

BACKGROUND & AIMS: Hepatic ischemia/reperfusion injury is a complication of liver surgery that involves mitochondrial dysfunction resulting from mitochondrial permeability transition pore (mPTP) opening. Cyclophilin D (PPIF or CypD) is a peptidyl-prolyl cis-trans isomerase that regulates mPTP opening in the inner mitochondrial membrane. We investigated whether and how recently created small-molecule inhibitors of CypD prevent opening of the mPTP in hepatocytes and the resulting effects in cell models and livers of mice undergoing ischemia/reperfusion injury. METHODS: We measured the activity of 9 small-molecule inhibitors of cyclophilins in an assay of CypD activity. The effects of the small-molecule CypD inhibitors or vehicle on mPTP opening were assessed by measuring mitochondrial swelling and calcium retention in isolated liver mitochondria from C57BL/6J (wild-type) and Ppif-/- (CypD knockout) mice and in primary mouse and human hepatocytes by fluorescence microscopy. We induced ischemia/reperfusion injury in livers of mice given a small-molecule CypD inhibitor or vehicle before and during reperfusion and collected samples of blood and liver for histologic analysis. RESULTS: The compounds inhibited peptidyl-prolyl isomerase activity (half maximal inhibitory concentration values, 0.2-16.2 µmol/L) and, as a result, calcium-induced mitochondrial swelling, by preventing mPTP opening (half maximal inhibitory concentration values, 1.4-132 µmol/L) in a concentration-dependent manner. The most potent inhibitor (C31) bound CypD with high affinity and inhibited swelling in mitochondria from livers of wild-type and Ppif-/- mice (indicating an additional, CypD-independent effect on mPTP opening) and in primary human and mouse hepatocytes. Administration of C31 in mice with ischemia/reperfusion injury before and during reperfusion restored hepatic calcium retention capacity and oxidative phosphorylation parameters and reduced liver damage compared with vehicle. CONCLUSIONS: Recently created small-molecule inhibitors of CypD reduced calcium-induced swelling in mitochondria from mouse and human liver tissues. Administration of these compounds to mice during ischemia/reperfusion restored hepatic calcium retention capacity and oxidative phosphorylation parameters and reduced liver damage. These compounds might be developed to protect patients from ischemia/reperfusion injury after liver surgery or for other hepatic or nonhepatic disorders related to abnormal mPTP opening.


Assuntos
/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Traumatismo por Reperfusão/prevenção & controle , Animais , Sinalização do Cálcio/efeitos dos fármacos , Células Cultivadas , /metabolismo , Citoproteção , Modelos Animais de Doenças , Humanos , Fígado/enzimologia , Fígado/patologia , Hepatopatias/enzimologia , Hepatopatias/genética , Hepatopatias/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias Hepáticas/enzimologia , Mitocôndrias Hepáticas/patologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Dilatação Mitocondrial/efeitos dos fármacos , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Transdução de Sinais
13.
Oxid Med Cell Longev ; 2019: 9549506, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205591

RESUMO

It has been demonstrated that vagus nerve stimulation (VNS) plays a protective role in ischemia/reperfusion (I/R) injury of various organs. The present study investigates the protective effect of VNS on hepatic I/R injury and the potential mechanisms. Male Sprague-Dawley rats were randomly allocated into three groups: the sham operation group (Sham; n = 6, sham surgery with sham VNS); the I/R group (n = 6, hepatic I/R surgery with sham VNS); and the VNS group (n = 6, hepatic I/R surgery plus VNS). The I/R model was established by 1 hour of 70% hepatic ischemia. Tissue samples and blood samples were collected after 6 hours of reperfusion. The left cervical vagus nerve was separated and stimulated throughout the whole I/R process. The stimulus intensity was standardized to the voltage level that slowed the sinus rate by 10%. VNS significantly reduced the necrotic area and cell death in I/R tissues. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were also decreased by VNS. In addition, VNS suppressed inflammation, oxidative stress, and apoptosis in I/R tissues. VNS significantly increased the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) in the liver. These data indicated that VNS may attenuate hepatic I/R injury by inhibiting inflammation, oxidative stress, and apoptosis possibly via the Nrf2/HO-1 pathway.


Assuntos
Modelos Animais de Doenças , Heme Oxigenase (Desciclizante)/metabolismo , Hepatopatias/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Traumatismo por Reperfusão/prevenção & controle , Estimulação do Nervo Vago/métodos , Animais , Apoptose , Heme Oxigenase (Desciclizante)/genética , Hepatopatias/etiologia , Hepatopatias/patologia , Masculino , Fator 2 Relacionado a NF-E2/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia
14.
Med Sci Monit ; 25: 3212-3220, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31041919

RESUMO

BACKGROUND Liver failure after resection for liver cancer is associated with increased patient mortality. This study aimed to investigate the mechanism of the protective effects of resveratrol, a natural plant-derived compound, on liver injury in a rat model of partial hepatectomy. MATERIAL AND METHODS Adult male Sprague-Dawley (SD) rats (n=60) were divided into the sham group (n=20), the liver resection group (n=20), and the liver resection plus resveratrol-treated group (n=20). Liver resection removed 2/3 of the liver resection; resveratrol was given at a dose of 30 mg/kg/day from one week before surgery until death. Liver injury was assessed by serum liver function tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl-transferase (γ-GT) and total bilirubin, histological examination of the rat liver, and liver cell apoptosis using the TUNEL assay. High mobility group box 1 (HMGB1) expression was measured by enzyme-linked immunoassay (ELISA). Sirtuin 1 (SIRT1) and acetylated HMGB1 (Ac-HMGB1) expression were detected by Western blot. Normal human liver cells and HepG2 liver cancer cells were incubated with acetylated HMGB1, and albumin production and ammonia elimination assays were performed. RESULTS Resveratrol reduced postoperative liver injury as shown by reduced ALT, AST, γ-GT, and total bilirubin levels, maintained liver structure, and reduced cell apoptosis. Resveratrol treatment reduced the expression and acetylation levels of HMGB1 via the SIRT1 signaling pathway. Resveratrol reversed Ac-HMGB1 induced dysfunction in liver cells cultured in vitro. CONCLUSIONS Resveratrol reduced liver damage after liver resection in a rat model by upregulating SIRT1 and reducing the acetylation of HMGB1.


Assuntos
Proteína HMGB1/metabolismo , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Acetilação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Células Hep G2 , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fígado/patologia , Fígado/cirurgia , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Hepatopatias/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para Cima
15.
Fish Shellfish Immunol ; 90: 338-348, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31075404

RESUMO

N-Carbamylglutamate (NCG), an analogue of N-acetylglutamate (NAG), can promote the synthesis of endogenous Arginine (Arg) in mammals, but not well studied in fish. This study was conducted to investigate the capacity of Arg endogenous synthesis by NCG, and the effects of various dietary NCG doses on growth performance, hepatic health and underlying nutrient regulation metabolism on ERK1/2-mTOR-S6K1 signaling pathway in Japanese seabass (Lateolabrax japonicus). Four experimental diets were prepared with NCG supplement levels of 0 (N0), 360 (N360), 720 (N720) and 3600 (N3600) mg/kg, in which N360 was at the maximum recommended level authorized by MOA, China in fish feed, and the N720 and N3600 levels were 2 and 10-fold of N360, respectively. Each diet was fed to 6 replicates with 30 Japanese seabass (initial body weight, IBW = 11.67 ±â€¯0.02 g) in each tank. The results showed that the dietary NCG supplementation had no significant effects on the SGR and morphometric parameters of Japanese seabass, but 360-720 mg/kg NCG inclusion promoted PPV, while the 10-fold (3600 mg/kg) overdose of NCG had remarkably negative effects with significantly reduced feed efficiency, PPV and LPV. We found that Japanese seabass can utilize 360-720 mg/kg NCG to synthesis Arg to improve the amino acid metabolism by increasing plasma Arg and up-regulating intestinal ASL gene expression. Increased plasma GST and decreased MDA indicated the improved antioxidant response. Dietary NCG inclusion decreased plasma IgM and down-regulated the mRNA levels of inflammation (TNF-α and IL8), apoptosis (caspase family) and fibrosis (TGF-ß1) related genes in the liver. The immunofluorescence examination revealed significantly decreased hepatic apoptosis and necrosis signals in the NCG groups. The ameliorated liver function and histological structure were closely related to the improved lipid metabolism parameters with decreased plasma VLDL and hepatic TG and NEFA accumulation, down-regulated fatty acid and cholesterol synthesis and simultaneously increased lipolysis gene mRNA levels, which regulated by inhibiting phosphorylation of ERK1/2-mTOR-S6K1 signaling pathway. Consuming 3600 mg/kg of dietary NCG is not safe for Japanese seabass culturing with the significantly increased FCR and decreased protein and lipid retention, and reduced plasma ALB. Accordingly, the observed efficacy and safety level of dietary NCG in the diet of Japanese seabass is 720 mg/kg.


Assuntos
Bass , Doenças dos Peixes/prevenção & controle , Glutamatos/metabolismo , Hepatopatias/veterinária , Doenças Metabólicas/veterinária , Ração Animal/análise , Animais , Apoptose/efeitos dos fármacos , Arginina/biossíntese , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Glutamatos/administração & dosagem , Hepatócitos/efeitos dos fármacos , Hepatopatias/imunologia , Hepatopatias/prevenção & controle , Doenças Metabólicas/imunologia , Doenças Metabólicas/prevenção & controle , Nutrientes/metabolismo , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos
16.
PLoS One ; 14(4): e0214471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943226

RESUMO

Increased global regulation and restrictions on the non-therapeutic use of antibiotics in the poultry industry means that there is a need to identify alternatives that prevent infection while still conveying the growth and performance benefits afforded by their use. Biochars are produced by the incomplete pyrolysis of organic materials, with reports of use as a feed supplement and activity against pathogenic bacteria. In the current study the dose-dependent effects of biochar dietary inclusion in layer diets at 1%, 2% and 4% w/w were investigated to determine a) the efficacy of biochar as an anti-pathogenic additive on the intestinal microbiota and b) the optimal inclusion level. Biochar inclusion for anti-pathogenic effects was found to be most beneficial at 2% w/w. Poultry pathogens such as Gallibacterium anatis and campylobacters, including Campylobacter hepaticus, were found to be significantly lower in biochar fed birds. A shift in microbiota was also associated with the incorporation of 2% w/w biochar in the feed in two large scale trials on two commercial layer farms. Biochar inclusion for anti-pathogenic effects was found to be most beneficial at 2% w/w. Differential effects of the timing of biochar administration (supplementation beginning at hatch or at point of lay) were also evident, with greater impact on community microbial structure at 48 weeks of age when birds were fed from hatch rather than supplemented at point of lay.


Assuntos
Ração Animal , Infecções por Campylobacter/veterinária , Campylobacter , Carvão Vegetal/química , Hepatopatias/veterinária , Doenças das Aves Domésticas/prevenção & controle , Ciências da Nutrição Animal , Animais , Infecções por Campylobacter/prevenção & controle , Galinhas/microbiologia , Suplementos Nutricionais , Feminino , Microbioma Gastrointestinal , Hepatopatias/microbiologia , Hepatopatias/prevenção & controle , Microbiota , Doenças das Aves Domésticas/microbiologia
17.
Complement Ther Med ; 43: 265-270, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30935541

RESUMO

OBJECTIVE: Gastrointestinal (GI) disorders are estimated to be frequent among general population. Various types of traditional and complementary therapies, primarily phytotherapy, can be used for prevention and treatment of many diseases and conditions, including GI complaints. Thus, the aim of this study was to investigate the patterns of use of medicinal herbs in treatment and prevention of GI disorders, together with their efficacy and safety. METHODS: A prospective, repeated cross-sectional, descriptive study was conducted in the form of a specifically created questionnaire, filled in by consumers and/or patients in pharmacies on the territory of Autonomous Province of Vojvodina, Republic of Serbia. All data were statistically analyzed in Microsoft Excel 2007. RESULTS: In the total number of 1137 patients, 10.4% declared themselves as consumers of phytopreparations for GI disorders. The most common diseases were constipation (44%) and dyspepsia (23%). The most frequently used preparations contained laxatives (with both anthraquinones and dietary fibers), artichoke and silymarin. Iberogast® was also frequently used. Pharmacists were the main source of recommendation for the most adequate herbal remedies. At the same time, phytopreparations were well tolerated, with no major side effects, and were evidently or presumably effective. CONCLUSIONS: Some mild and moderate GI disorders seem to be treated frequently with phytopreparatons. Various herbal remedies are well accepted by patients, and the phytopreparations seem to have favorable ratio of safety and efficacy. Further integration into conventional medicine will improve the quality of the products used and provide a rational plan of use of medicinal plants.


Assuntos
Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/prevenção & controle , Hepatopatias/tratamento farmacológico , Hepatopatias/prevenção & controle , Plantas Medicinais/química , Adulto , Estudos Transversais , Cynara scolymus/química , Feminino , Humanos , Laxantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Estudos Prospectivos , Sérvia , Silimarina/uso terapêutico , Inquéritos e Questionários
18.
Clin Liver Dis ; 23(2): 279-291, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30947877

RESUMO

Intestinal failure-associated liver disease (IFALD) is characterized by either liver steatosis or cholestasis and may develop in patients on long-term home parenteral nutrition for chronic intestinal failure. The pathogenesis of IFALD is multifactorial and includes gastrointestinal disease-related, parenteral nutrition-related, and systemic-related factors. Alteration of bile acid enterohepatic circulation, gut microbiome, and intestinal permeability, seem to be the main mechanisms. Patients forced to a total oral fasting regimen are at greater risk. Parenteral nutrition overfeeding and/or of soybean-based lipid emulsion may be contributing factors. Prevention and treatment are based on avoiding and promptly treating all the risk factors.


Assuntos
Enteropatias/complicações , Enteropatias/fisiopatologia , Hepatopatias/etiologia , Hepatopatias/terapia , Ácidos e Sais Biliares/metabolismo , Microbioma Gastrointestinal , Humanos , Hepatopatias/diagnóstico , Hepatopatias/prevenção & controle , Nutrição Parenteral/efeitos adversos
19.
Am J Clin Nutr ; 109(4): 1038-1050, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30882140

RESUMO

BACKGROUND: Fish oil (FO) intravenous lipid emulsions (ILEs) are used as a monotherapy to treat parenteral nutrition (PN)-associated liver disease and provide essential fatty acids (EFAs) needed to sustain growth and prevent EFA deficiency (EFAD). Studies have suggested that medium-chain triglycerides (MCTs) and α-tocopherol have anti-inflammatory properties. OBJECTIVE: The purpose of this study was to test whether FO-ILEs containing MCTs and/or additional α-tocopherol decrease the inflammatory response to an endotoxin challenge compared with FO-ILE alone and preserve the ability to prevent PN-induced liver injury in mice. METHODS: A murine model of PN-induced hepatosteatosis was used to compare the effects of ILEs formulated in the laboratory containing varying ratios of FO and MCTs, and subsequently FO- and 50:50 FO:MCT-ILE plus 500 mg/L α-tocopherol (FO + AT and 50:50 + AT, respectively). C57BL/6 mice receiving unpurified diet (UPD), PN-equivalent diet (PN) + saline, and PN + soybean oil (SO)-ILE served as controls. After 19 d, mice received an intraperitoneal saline or endotoxin challenge 4 h before being killed. Serum and livers were harvested for histologic analysis, fatty acid profiling, and measurement of systemic inflammatory markers (tumor necrosis factor-α, interleukin-6). RESULTS: All ILEs were well tolerated and prevented biochemical EFAD. Livers of mice that received saline and SO developed steatosis. Mice that received 30:70 FO:MCT developed mild hepatosteatosis. All other FO-containing ILEs preserved normal hepatic architecture. Mice that received FO- or SO-ILE had significantly elevated systemic inflammatory markers after endotoxin challenge compared with UPD-fed controls, whereas 50:50 FO:MCT, 30:70 FO:MCT, FO + AT, and 50:50 + AT groups had significantly lower inflammatory markers similar to those seen in UPD-fed controls. CONCLUSIONS: Mixed FO/MCT and the addition of α-tocopherol to FO improved the inflammatory response to endotoxin challenge compared with FO-ILE alone while still preventing PN-induced liver injury and EFAD in mice. There was no synergistic relation between α-tocopherol and MCTs.


Assuntos
Anti-Inflamatórios/administração & dosagem , Emulsões Gordurosas Intravenosas/administração & dosagem , Óleos de Peixe/administração & dosagem , Hepatopatias/prevenção & controle , Nutrição Parenteral/efeitos adversos , Triglicerídeos/administração & dosagem , Triglicerídeos/química , alfa-Tocoferol/administração & dosagem , Animais , Anti-Inflamatórios/química , Modelos Animais de Doenças , Emulsões Gordurosas Intravenosas/química , Óleos de Peixe/química , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Hepatopatias/etiologia , Hepatopatias/genética , Hepatopatias/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
20.
Amino Acids ; 51(5): 795-803, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30879149

RESUMO

We aimed to evaluate whether two methionine-related compounds, S-adenosylmethionine (SAM), and selenomethionine (SM), could lessen liver damage induced by regurgitated bile in a model of rat bile duct ligation (BDL). Hepatoprotective potentials of S-adenosylmethionine and selenomethionine were estimated based on the changes of serum liver damage parameters (aminotransferases, alkaline phosphatase, gamma-glutamyltranspeptidase and lactate dehydrogenase activity, and bilirubin concentration), tissue oxidative [xanthine oxidase (XO) and catalase activity, thiobarbituric acid reactive substances (TBARS) levels] and inflammatory [tumor necrosis factor-alfa (TNF-α) concentration] parameters, and morphological liver tissue alterations that follow cholestasis. The treatment regimens proved themselves able to prevent significant liver damage induced by cholestasis. Both SAM and SM decreased XO activity and TBARS levels and increased catalase activity, while only SM significantly reduced TNF-α concentration. Morphological changes related to bile-induced liver damage were also found to be partially diminished by SAM and SM. In view of the mechanisms of action of the two tested methionine-derived compounds, one might say that SM predominantly acted as an antioxidant, while SAM exerted its activity by potentially modulating different gene expression and protein structures. It is also worth mentioning that this is the first study (to the best of our knowledge) that dealt with the effects of SM on BDL-induced liver injury in rats and of the findings that speak favorably of this powerful antioxidant.


Assuntos
Colestase/complicações , Hepatopatias/prevenção & controle , S-Adenosilmetionina/farmacologia , Selenometionina/farmacologia , Animais , Catalase/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico , Xantina Oxidase/metabolismo
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