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1.
Rev. cuba. med ; 60(3): e1678, 2021. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1347511

ABSTRACT

Introducción: La enfermedad por depósito graso no alcohólica constituye una pandemia del mundo contemporáneo. Su espectro silente atraviesa estadios de cronicidad y puede llegar a la cirrosis hepática y sobre esta pudiera desarrollarse un hepatocarcinoma. No existen tratamientos y solo se puede actuar sobre los factores de riesgo. Objetivo: Evaluar el efecto citohepatoprotector y antifibrótico del propóleos rojo cubano oral en pacientes con esteatohepatitis no alcohólica. Métodos: Se realizó un estudio longitudinal prospectivo en pacientes seleccionados de las consultas de Gastroenterología, Endocrinología y Medicina Interna del Hospital Clínico Quirúrgico Hermanos Ameijeiras durante el periodo de abril 2017 a abril 2018. El universo de estudio fue de 120 pacientes con diagnóstico imagenológico de hígado graso. La muestra quedó conformada por 70 pacientes con diagnóstico de hígado graso, y que cumplieron criterios de inclusión y exclusión. Las pruebas estadísticas aplicadas fueron análisis de frecuencia y porcentaje para las variables demográficas. La prueba T para las muestras relacionadas evaluó el comportamiento enzimático al inicio y al final del tratamiento y los cambios elastográficos fueron analizados mediante test de Kappa y porcentaje. Resultados: Las variables bioquímicas estudiadas mostraron una disminución estadísticamente significativa al final del tratamiento. Los cambios elastográficos al final del estudio evidenciaron la efectividad del tratamiento, en el cual el 91,4 por ciento de los pacientes evolucionaron hacia el menor grado de fibrosis. Conclusiones: El propóleos rojo cubano demostró ser un apifármaco con acción citohepatoprotectora y antifibrótica de valor terapéutico(AU)


Introduction: Nonalcoholic fat deposition disease is a pandemic in the contemporary world. Its silent spectrum goes through stages of chronicity and it can reach liver cirrhosis and on this a hepatic carcinoma could develop. There are no treatments and medical handling can act on only risk factors. Objective: To evaluate cytohepatoprotective and antifibrotic effect of oral Cuban red propolis in patients with nonalcoholic steatohepatitis. Methods: A prospective longitudinal study was carried out in selected patients from the Gastroenterology, Endocrinology and Internal Medicine consultations at Hermanos Ameijeiras Clinical Surgical Hospital from April 2017 to April 2018. The study universe was 120 patients with imaging diagnosis of fatty liver. The sample consisted of 70 patients with fatty liver diagnosis, who met the inclusion and exclusion criteria. Frequency and percentage analysis for the demographic variables were the statistical tests applied. The T test for the related samples evaluated the enzymatic behavior at the beginning and at the end of the treatment and the elastography changes were analyzed using Kappa and percentage tests. Results: The biochemical variables studied showed statistically significant decrease at the end of the treatment, which evidenced the effectiveness of the treatment. 91.4 percent of the patients progressed to a lower degree of fibrosis. Conclusions: Cuban red propolis proved to be a therapeutic drug with cytohepathoprotective and antifibrotic action(AU)


Subject(s)
Humans , Elasticity Imaging Techniques/methods , Apitherapy , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Prospective Studies , Risk Factors , Longitudinal Studies
2.
Rev. chil. endocrinol. diabetes ; 14(1): 7-13, 2021. tab, ilus
Article in Spanish | LILACS | ID: biblio-1146465

ABSTRACT

INTRODUCCIÓN: La enfermedad del hígado graso no alcohólico (EHGNA) es la forma más común de enfermedad hepática. A nivel celular se caracteriza por la acumulación de triglicéridos (TG) en forma de gotas lipídicas (GL) dando lugar a esteatosis e inflamación. Entre los factores relevantes para la síntesis de TG se encuentran las enzimas DGAT1/2 que catalizan la etapa final de la síntesis de TG, y la proteína FABP4 que transporta lípidos intracelulares y se expresa en modelos de enfermedad hepática dependiente de obesidad. Por otra parte, TNF-α es una reconocida citoquina involucrada en el proceso inflamatorio en la EHGNA. La medicina popular del norte de Chile ha utilizado la planta Lampaya medicinalis Phil. (Verbenaceae) para el tratamiento de algunas enfermedades inflamatorias. OBJETIVO: Evaluar el efecto de un extracto hidroalcóholico de lampaya (EHL) sobre la esteatosis y expresión de marcadores de inflamación en hepatocitos tratados con ácidos grasos. Diseño experimental: Estudio in vitro en cultivos de la línea celular humana HepG2 tratadas con ácido oleico (AO) y ácido palmítico (AP). MÉTODOS: Se incubó hepatocitos HepG2 con AO/AP por 24 horas en presencia o no de EHL. Se evaluó la presencia de GL y el contenido de TG intracelulares por Oil Red O y Nile Red, respectivamente. La expresión de DGAT1/2, FABP4 y TNF-α fue evaluada por qPCR. RESULTADOS: Los hepatocitos tratados con AO/AP mostraron un aumento en las GL y TG, así como una mayor expresión de DGAT2 en comparación al control. El cotratamiento con EHL revirtió los efectos inducidos por AO/AP. CONCLUSIONES: EHL revierte el incremento en las GL, TG y en la expresión de DGAT2 inducido por AO/AP en células HepG2. Estos hallazgos sugieren un efecto hepatoprotector de la Lampaya contra la esteatosis, y apoyarían su uso complementario en el tratamiento de patologías con componente inflamatorio como la EHGNA.


Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. At the cellular level, it is characterized by the accumulation of triglycerides (TG) in the form of lipid droplets (LD), which leads to steatosis and inflammation. Among relevant factors for TG synthesis are the enzymes DGAT1/2 catalyzing the final stage of TG synthesis, and the protein FABP4 which transports intracellular lipids and is expressed in cell models of obesity-dependent liver disease. Additionally, TNF-α is a cytokine involved in the inflammatory process associated to NAFDL. Lampaya medicinalis Phil. (Verbenaceae) is a plant used in folk medicine in northern Chile to treat some inflammatory diseases. OBJECTIVE: To evaluate the effect of the hydroalcoholic extract of lampaya (HEL) on steatosis and the expression of inflammatory markers in hepatocytes treated with fatty acids. Study design: In vitro study in cultures of the human HepG2 cell line treated with oleic acid (OA) and palmitic acid (PA). METHODS: HepG2 hepatocytes were incubated with OA/PA for 24 hours in the presence and absence of HEL. The formation of LD and the accumulation of intracellular TG were assessed by Oil Red O and Nile Red, respectively. The expression of DGAT1/2, FABP4 and TNF-α was assessed by qPCR. RESULTS: The treatment with OA/PA increased the levels of LD and TG as well as the expression of DGAT2 in HepG2 hepatocytes compared to control cells. HEL cotreatment counteracted OA/PA-induced effects. CONCLUSIONS: HEL prevents the increase in LD and TG levels and DGAT2 expression induced by OA/PA in HepG2 cells. These findings suggest that lampaya may have a protective effect against hepatic steatosis, which would support its complementary use in the treatment of pathologies associated with inflammation, such as NAFLD.


Subject(s)
Humans , Plant Extracts/pharmacology , Hepatocytes/drug effects , Verbenaceae/chemistry , Non-alcoholic Fatty Liver Disease/drug therapy , Triglycerides/analysis , In Vitro Techniques , Plant Extracts/therapeutic use , Cell Survival , Polymerase Chain Reaction , Cell Culture Techniques , Oleic Acid , Ethanol/chemistry , Hep G2 Cells/drug effects , Inflammation
3.
Braz. j. med. biol. res ; 54(10): e11391, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285650

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,β-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.


Subject(s)
Animals , Male , Rabbits , Insulin Resistance , Non-alcoholic Fatty Liver Disease/prevention & control , Non-alcoholic Fatty Liver Disease/drug therapy , Oleanolic Acid/analogs & derivatives , Sterol Regulatory Element Binding Protein 1 , AMP-Activated Protein Kinases , Diet, High-Fat/adverse effects , Mechanistic Target of Rapamycin Complex 1 , Liver , Mice, Inbred C57BL
4.
Journal of Integrative Medicine ; (12): 545-554, 2021.
Article in English | WPRIM | ID: wpr-922528

ABSTRACT

OBJECTIVE@#To investigate effects of berberine (BBR) on cholesterol synthesis in HepG2 cells with free fatty acid (FFA)-induced steatosis and to explore the underlying mechanisms.@*METHODS@#A steatosis cell model was induced in HepG2 cell line fed with FFA (0.5 mmol/L, oleic acid:palmitic acid = 2:1), and then treated with three concentrations of BBR; cell viability was assessed with cell counting kit-8 assays. Lipid accumulation in cells was observed through oil red O staining and total cholesterol (TC) content was detected by TC assay. The effects of BBR on cholesterol synthesis mediators were assessed by Western blotting and quantitative polymerase chain reaction. In addition, both silent information regulator 1 (SIRT1) and forkhead box transcription factor O1 (FoxO1) inhibitors were employed for validation.@*RESULTS@#FFA-induced steatosis was successfully established in HepG2 cells. Lipid accumulation and TC content in BBR groups were significantly lower (P < 0.05, P < 0.01), associated with significantly higher mRNA and protein levels of SIRT1(P < 0.05, P < 0.01), significantly lower sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy 3-methylglutaryl-CoA reductase levels (P < 0.05, P < 0.01), as well as higher Acetyl-FoxO1 protein level (P < 0.05, P < 0.01) compared to the FFA only group. Both SIRT1 inhibitor SIRT1-IN-1 and FoxO1 inhibitor AS1842856 blocked the BBR-mediated therapeutic effects. Immunofluorescence showed that the increased SIRT1 expression increased FoxO1 deacetylation, and promoted its nuclear translocation.@*CONCLUSION@#BBR can mitigate FFA-induced steatosis in HepG2 cells by activating SIRT1-FoxO1-SREBP2 signal pathway. BBR may emerge as a potential drug candidate for treating nonalcoholic hepatic steatosis.


Subject(s)
Berberine/pharmacology , Cholesterol , Forkhead Box Protein O1/genetics , Humans , Non-alcoholic Fatty Liver Disease/drug therapy , Sirtuin 1/genetics , Sterol Regulatory Element Binding Proteins
5.
Journal of Integrative Medicine ; (12): 428-438, 2021.
Article in English | WPRIM | ID: wpr-888771

ABSTRACT

OBJECTIVE@#High-fat diet (HFD) and inflammation are two key contributors to nonalcoholic fatty liver disease (NAFLD). Shenling Baizhu powder (SLBZP), a classical herbal compound, has been successfully used to alleviate NAFLD. However, its specific mechanisms are not fully understood. In this study, we assessed the anti-NAFLD effect of SLBZP in vivo.@*METHODS@#Rats were fed an HFD with or without SLBZP or with probiotics. At the end of week 16, an echo magnetic resonance imaging (EchoMRI) body composition analyser was used to quantitatively analyse body composition; a micro-computed tomography (micro-CT) imaging system was used to evaluate whole body and liver fat; and the Moor full-field laser perfusion imager 2 was used to assess liver microcirculation, after which, all rats were sacrificed. Then, biochemical indicators in the blood and the ultrastructure of rat livers were evaluated. Protein expression related to the liver Toll-like receptor 4 (TLR4)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) signalling pathway was assessed using Western blot analysis. Further, high-throughput screening of 29 related inflammatory factors in liver tissue was performed using a cytokine array.@*RESULTS@#SLBZP supplementation reduced body weight, serum free fatty acid, and insulin resistance index (P < 0.05). It also ameliorated liver microcirculation and ultrastructural abnormalities. EchoMRI and micro-CT quantitative analyses showed that treatment with SLBZP reduced fat mass and visceral fat (P < 0.05 and P < 0.01, respectively). In addition, SLBZP decreased the expression of lipopolysaccharide (LPS)-activated TLR4/NLRP3 signalling pathway-related proteins and altered the expression levels of some inflammatory cytokines in liver tissues.@*CONCLUSION@#SLBZP can inhibit NLRP3 inflammasome activation and interleukin-1β release by suppressing LPS-induced TLR4 expression in rats with HFD-induced NAFLD. Thus, SLBZP may be beneficial for the prevention and treatment of inflammatory damage and associated diseases.


Subject(s)
Animals , Liver , NLR Family, Pyrin Domain-Containing 3 Protein , Non-alcoholic Fatty Liver Disease/drug therapy , Powders , Rats , Toll-Like Receptor 4 , X-Ray Microtomography
6.
Arq. gastroenterol ; 56(2): 184-190, Apr.-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1019457

ABSTRACT

ABSTRACT BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.


RESUMO CONTEXTO: Atualmente, o tratamento farmacológico da doença hepática gordurosa não alcoólica (DHGNA) ainda é limitado e baseia-se no tratamento de condições associadas às comorbidades. O estresse oxidativo e a resistência à insulina são os mecanismos que parecem estar mais envolvidos em sua patogênese. OBJETIVO: Avaliar a eficácia da N-acetilcisteína (NAC) em associação à metformina (MTF) e/ou ácido ursodesoxicólico (UDCA) no tratamento da EHNA. MÉTODOS: Estudo randomizado, multicêntrico e aberto, conduzido por 48 semanas. Incluiu pacientes com esteato-hepatite não alcoólica (EHNA) comprovada por biópsia. Os pacientes foram distribuídos aleatoriamente em três grupos: NAC (1,2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/dia) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/dia) (n=13); NAC (1,2 g) + MTF (850-1500 mg/dia) (n=14) durante 48 semanas. Os dados clínicos, laboratoriais e as segundas biópsias hepáticas foram realizados após 48 semanas. RESULTADOS - Um total de 53 pacientes foram avaliados; 17 (32,1%) eram do sexo masculino; idade mediana de ±54 (IQR=15, 21-71) anos. No baseline, nenhuma diferença foi observada entre os grupos de acordo com parâmetros clínicos e histológicos. Os grupos diferiram apenas em colesterol, LDL e triglicerídeos. Não foram encontradas diferenças significativas nos parâmetros bioquímicos e histológicos entre os três grupos após 48 semanas de tratamento. Contudo, na análise intragrupos (intenção de tratar) comparando características histológicas e bioquímicas, houve melhora significativa no grau de esteatose (P=0,014), balonização (P=0,027) e, consequentemente, no NAFLD Activity Score (NAS) (P=0,005), e nos níveis de ALT no final do tratamento apenas no grupo NAC+MTF. Nenhuma evidência significativa de modificaçãona fibrose hepática pôde ser observada em nenhum dos grupos. CONCLUSÃO: - Este estudo multicêntrico sugere que a associação de NAC+MTF poderia reduzir a atividade da doença hepática em pacientes com EHNA. Esses dados estimulam estudos adicionais controlados com essa terapia para esses pacientes.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Aged , Young Adult , Acetylcysteine/administration & dosage , Ursodeoxycholic Acid/administration & dosage , Non-alcoholic Fatty Liver Disease/drug therapy , Metformin/administration & dosage , Treatment Outcome , Drug Therapy, Combination , Middle Aged
7.
Rev. Assoc. Med. Bras. (1992) ; 65(1): 33-37, Jan. 2019. tab
Article in English | LILACS | ID: biblio-985003

ABSTRACT

SUMMARY OBJECTIVE To investigate the clinical efficacy and the possible mechanisms of saxagliptin in the treatment of type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD). METHODS A total of 95 T2DM and NAFLD patients were randomly divided into group A (saxagliptin group), group B (glimepiride group), and group C (glimepiride combined with polyene phosphatidylcholine group). RESULTS After intervention treatment for 24 w, body mass index (BMI), waist-to-hip ratio (WHR), glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and quantitative detection of liver steatosis of study subjects were observed, the action of liver steatosis in subjects of groups A and C were significantly different from those of group B; however, there were no differences between groups A and C. The FINS, HOMA-IR, and IL-6 of subjects in group A was lower than those in groups B and C; however, there were no significant differences between the latter two groups. CONCLUSION For T2DM combined with NAFLD patients, the saxagliptin treatment could not only effectively control blood glucose but also attenuate insulin resistance and inflammatory injury of the liver to improve fatty liver further.


RESUMO OBJETIVO Investigar a eficácia clínica e os possíveis mecanismos da saxagliptina no tratamento do diabetes mellitus tipo 2 (DM2) associado à doença hepática gordurosa não alcoólica (DHGNA). MÉTODOS Um total de 95 DM2 combinados com pacientes com DHGNA foram aleatoriamente divididos em grupo A (grupo saxagliptina), grupo B (grupo glimepirida) e grupo C (glimepirida combinado com grupo fosfatidilcolina polienizada). RESULTADOS Após a intervenção tratamento por 24 w, índice de massa corporal (IMC), relação cintura-quadril (RCQ), hemoglobina glicada (HbA1c), glicemia de jejum (FPG), insulina de jejum (Fins), avaliação do modelo homeostático de insulina resistência (Homa-IR), interleucina-6 (IL-6), triglicérides (TG), colesterol total (CT), alanina aminotransferase (ALT), aspartato aminotransferase (AST), γ-glutamiltransferase (γ-GT) e detecção de esteatose hepática dos sujeitos do estudo foram observados. Ação de esteatose hepática de indivíduos nos grupos A e C foram significativamente diferentes do grupo B; no entanto, não houve diferenças entre os grupos A e C. Os grupos Fins, Homa-IR e IL-6 dos participantes do grupo A foram menores que os dos grupos B e C; no entanto, não houve diferenças significativas entre os dois últimos grupos. CONCLUSÃO Para o DM2 combinado com pacientes com DHGNA, o tratamento com saxagliptina pode não apenas controlar efetivamente a glicemia, mas também atenuar a resistência à insulina e a lesão inflamatória do fígado para melhorar ainda mais o fígado gorduroso.


Subject(s)
Humans , Male , Female , Phosphatidylcholines/administration & dosage , Sulfonylurea Compounds/administration & dosage , Adamantane/analogs & derivatives , Diabetes Mellitus, Type 2/drug therapy , Non-alcoholic Fatty Liver Disease/drug therapy , Hypoglycemic Agents/administration & dosage , Blood Glucose , Insulin Resistance , Adamantane/administration & dosage , Body Mass Index , Treatment Outcome , Diabetes Mellitus, Type 2/complications , Dipeptides/administration & dosage , Non-alcoholic Fatty Liver Disease/complications , Middle Aged
8.
Braz. j. med. biol. res ; 51(8): e7299, 2018. graf
Article in English | LILACS | ID: biblio-951744

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with metabolic syndrome and can lead to life-threatening complications like hepatic carcinoma and cirrhosis. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist antidiabetic drug, has the capacity to overcome insulin resistance and attenuate hepatic steatosis but the specific underlying mechanism is unclear. This study was designed to investigate the underlying molecular mechanisms of exenatide therapy on NAFLD. We used in vivo and in vitro techniques to investigate the protective effects of exenatide on fatty liver via fat mass and obesity associated gene (FTO) in a high-fat (HF) diet-induced NAFLD animal model and related cell culture model. Exenatide significantly decreased body weight, serum glucose, insulin, insulin resistance, serum free fatty acid, triglyceride, total cholesterol, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in HF-induced obese rabbits. Histological analysis showed that exenatide significantly reversed HF-induced lipid accumulation and inflammatory changes accompanied by decreased FTO mRNA and protein expression, which were abrogated by PI3K inhibitor LY294002. This study indicated that pharmacological interventions with GLP-1 may represent a promising therapeutic strategy for NAFLD.


Subject(s)
Animals , Male , Rabbits , Peptides/pharmacology , Venoms/pharmacology , Protective Agents/pharmacology , Fatty Liver/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/drug effects , Blood Glucose/analysis , Body Weight/drug effects , In Vitro Techniques , Gene Expression Regulation/drug effects , Morpholines/metabolism , Chromones/metabolism , Disease Models, Animal , Eating/drug effects , Enzyme Inhibitors/metabolism , Fatty Liver/pathology , Diet, High-Fat , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Exenatide , Insulin/blood , Malondialdehyde/analysis , Obesity/metabolism
9.
Int. j. morphol ; 35(1): 345-350, Mar. 2017. ilus
Article in English | LILACS | ID: biblio-840976

ABSTRACT

Non-alcoholic fatty liver induces many complications to the liver tissue and also serum related parameters. Medicinal plants are the safe therapeutic strategy for the treatment of diseases. In this regards, the present study was conducted to evaluate the effect of Tribulus terrestris (T. terrestris) extract on non-alcoholic fatty liver in rats. In this experimental study, thirty male Wistar rats were divided into five groups (n=6). Animals in experimental groups were received high fructose diet (70 %) (HDF) daily alone or in combined with daily intraperitoneal injection of 500, 700 and 1000 mg/kg extract of T. terrestris. Control group of rats was feed with standard chow. The serum levels of biomarkers of liver and serum lipid profiles were assessed, also histopathological examination of liver tissue done. Data were analyzed using One-way ANOVA method followed by Tukey's post-hoc multiple comparison test and P<0.05 was considered statistically significant. There were significant improvements for biomarkers of liver tissue (P<0.05) and serum lipid profiles (P<0.01) in the HFD-fed rats that were treated with T. terrestris extract compare to HFD-fed group. In addition, accumulation of lipids in hepatocytes was significantly reduced in the HFD-fed + extract administrated groups in comparison to HFD-fed rats (P<0.01). T. terrestris extract has protective effects against non-alcoholic fatty liver by changing biomarkers of liver tissue, serum lipid profiles and histopathological anomalies of liver tissue, to normal range.


El hígado graso no alcohólico induce muchas complicaciones al tejido hepático y también en ciertos parámetros relacionados con el suero. Las plantas medicinales son la estrategia terapéutica segura para el tratamiento de enfermedades. En este sentido, el presente estudio se realizó para evaluar el efecto del extracto de Tribulus terrestris (T. terrestris) sobre el hígado graso no alcohólico en ratas. En este estudio experimental se dividieron 30 ratas macho Wistar en cinco grupos (n = 6). Los animales de los grupos experimentales recibieron dietas altas en fructosa (70 %) (HDF) al día o en combinación con inyección intraperitoneal diaria de 500, 700 y 1000 mg / kg de extracto de T. terrestris. El grupo control de ratas fue alimentado con alimento estándar. Se evaluaron los niveles séricos de biomarcadores hepáticos y perfiles de lípidos séricos, así como un examen histopatológico del tejido hepático. Los datos se analizaron utilizando el método ANOVA de una vía seguido de la prueba de comparación múltiple post-hoc de Tukey y el P<0,05 se consideró estadísticamente significativo. Hubo mejoras significativas en los biomarcadores del tejido hepático (P <0,05) y en los perfiles de lípidos séricos (P <0,01) en las ratas alimentadas con HFD que se trataron con extrato de T. terrestris comparado con el grupo alimentado con HFD. Además, la acumulación de lípidos en los hepatocitos se redujo significativamente en los grupos alimentados con HFD + extracto, en comparación con las ratas alimentadas con HFD (P <0,01). El extracto de T. terrestris tiene efectos protectores sobre el hígado graso no alcohólico, provocando modificaciones en los marcadores biológicos del tejido hepático, los perfiles lipídicos del suero y las anomalías histopatológicas del tejido hepático, hasta un rango normal.


Subject(s)
Animals , Male , Rats , Non-alcoholic Fatty Liver Disease/drug therapy , Plant Extracts/therapeutic use , Tribulus/therapeutic use , Tribulus/chemistry , Plant Extracts/administration & dosage , Rats, Wistar , Tribulus/administration & dosage
10.
An. bras. dermatol ; 91(6): 781-789, Nov.-Dec. 2016.
Article in English | LILACS | ID: biblio-837982

ABSTRACT

Abstract During the last decade, different studies have converged to evidence the high prevalence of comorbidities in subjects with psoriasis. Although a causal relation has not been fully elucidated, genetic relation, inflammatory pathways and/or common environmental factors appear to be underlying the development of psoriasis and the metabolic comorbidities. The concept of psoriasis as a systemic disease directed the attention of the scientific community in order to investigate the extent to which therapeutic interventions influence the onset and evolution of the most prevalent comorbidities in patients with psoriasis. This study presents scientific evidence of the influence of immunobiological treatments for psoriasis available in Brazil (infliximab, adalimumab, etanercept and ustekinumab) on the main comorbidities related to psoriasis. It highlights the importance of the inflammatory burden on the clinical outcome of patients, not only on disease activity, but also on the comorbidities. In this sense, systemic treatments, whether immunobiologicals or classic, can play a critical role to effectively control the inflammatory burden in psoriatic patients.


Subject(s)
Humans , Psoriasis/drug therapy , Antibodies, Monoclonal/therapeutic use , Cardiovascular Diseases/drug therapy , Comorbidity , Risk Factors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Metabolic Syndrome/drug therapy , Diabetes Mellitus/drug therapy , Dyslipidemias/drug therapy , Obesity, Abdominal/drug therapy , Non-alcoholic Fatty Liver Disease/drug therapy , Hypertension/drug therapy
11.
Acta cir. bras ; 31(11): 706-713, Nov. 2016. tab, graf
Article in English | LILACS | ID: biblio-827661

ABSTRACT

ABSTRACT PURPOSE: To investigate the effect of curcumin on visfatin and zinc-α2-glycoprotein (ZAG) expression levels in rats with non-alcoholic fatty liver disease (NAFLD). METHODS: Fifty-six male rats were randomly divided into a control group (n=16) and model group (n=40) and were fed on a normal diet or a high-fat diet, respectively. Equal volumes of sodium carboxymethyl cellulose (CMC) were intragastrically administered to the control group for 4 weeks. At the end of the 12th week, visfatin and ZAG protein expression levels were examined by immunohistochemistry. Visfatin mRNA levels were measured by semi-quantitative reverse transcription polymerase chain reaction. RESULTS: Compared with the control group, the model group showed significantly increased expression of visfatin in liver tissue (P < 0.01) and significantly decreased expression of ZAG (P < 0.01). These effects were ameliorated by curcumin treatment. CONCLUSIONS: Visfatin and zinc-α2-glycoprotein may be involved in the pathogenesis of NAFLD. Treatment of NAFLD in rats by curcumin may be mediated by the decrease of visfatin and the increase of non-alcoholic fatty liver disease.


Subject(s)
Animals , Male , Rats , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Curcumin/therapeutic use , Seminal Plasma Proteins/metabolism , Nicotinamide Phosphoribosyltransferase/metabolism , Fatty Acids/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Triglycerides/blood , Random Allocation , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Cholesterol/blood , Rats, Sprague-Dawley , Curcumin/administration & dosage , Alanine Transaminase/blood , Disease Models, Animal , Drug Evaluation, Preclinical , Non-alcoholic Fatty Liver Disease/drug therapy , Liver/pathology , Antioxidants/administration & dosage , Antioxidants/therapeutic use
12.
Gastroenterol. latinoam ; 27(supl.1): S55-S59, 2016. ilus, tab, graf
Article in Spanish | LILACS | ID: biblio-907655

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) represents an increasing health problem in Chile and worldwide. In some cases NAFLD presents with a progressive form that can lead to liver fibrosis, cirrhosis and hepatocellular carcinoma. Current pharmacological therapies (pioglitazone and vitamin E) show limited response and are associated to significant adverse effects. During recent years several novel and promising pharmacological therapies have been developed to prevent fibrosis, liver cirrhosis and reduce liver related deaths. The present article summarizes some of these promising strategies, including reported efficacy in clinical trials and associated adverse effects. Hopefully in the near future these new therapies will help to improve NAFLD management and reduce liver related complications.


El hígado graso no alcohólico (HGNA) es un creciente problema de salud pública en Chile y el mundo. En un subgrupo de sujetos, el HGNA puede presentarse con un fenotipo de daño hepático progresivo que puede evolucionar a fibrosis progresiva, cirrosis y carcinoma hepatocelular. Las estrategias farmacológicas actuales (pioglitazona y vitamina E) presentan eficacia limitada y no están exentas de efectos adversos. Durante los últimos años se han desarrollado múltiples estrategias farmacológicas novedosas y promisorias que buscan evitar la progresión hacia cirrosis y reducir la mortalidad de causa hepática. El presente artículo resume los principales nuevos fármacos, los efectos beneficiosos reportados y sus efectos adversos. Es de esperar que en un futuro próximo estas terapias permitan cambiar el pronóstico de nuestros pacientes con HGNA.


Subject(s)
Humans , Chenodeoxycholic Acid/analogs & derivatives , Chenodeoxycholic Acid/therapeutic use , Liraglutide/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Propionates/therapeutic use , Chalcones/therapeutic use , Liver Cirrhosis/prevention & control
13.
Med. interna (Caracas) ; 31(4): 177-185, 2015. ilus
Article in Spanish | LILACS, LIVECS | ID: biblio-1009637

ABSTRACT

El Hígado graso no alcohólico (HGNA) se define como la infiltración grasa del hígado mayor al 5% de su peso incluyendo un amplio espectro de trastornos hepáticos que van desde la esteatosis simple hasta la esteatohepatitis pudiendo progresar a fibrosis, cirrosis, carcinoma hepatocelular y muerte. Para establecer el diagnóstico deben encontrarse hallazgos histológicos o imagenológicos, excluirse una causa secundaria de esteatosis y existir asociación con el Síndrome metabólico, en donde la Resistencia a la insulina es la piedra angular en su fisiopatología. Su prevalencia va en aumento de la mano con la epidemia de la obesidad a nivel mundial. La biopsia hepática sigue siendo el patrón de oro, sin embargo han surgido marcadores serológicos como índices predictivos de fibrosis así como métodos imagenológicos para lograr de manera no invasiva seleccionar a aquellos pacientes candidatos a biopsia hepática. El tratamiento de elección siguen siendo los cambios en el estilo de vida. La Vitamina E y las Tiazolidinedionas son los únicos que han demostrado evidencia en Ensayos Clínicos Controlados. Otros medicamentos serán discutidos así como drogas promisorias(AU)


Non-alcoholic fatty liver disease (NAFLD) is defined as fatty infiltration of the liver that is more than 5% of its weight including a wide spectrum of liver disorders ranging from simple steatosis to steatohepatitis, which can progress to fibrosis, cirrhosis, hepatocellular carcinoma and death. To establish the diagnosis histological or imaging findings to exclude a secondary cause of steatosis and have an association with metabolic syndrome, where insulin resistance is a cornerstone in its pathophysiology. Its prevalence is increasing with the obesity epidemic worldwide. Liver biopsy remains the gold standard; however serological markers have emerged as predictive indices of fibrosis and imaging methods to achieve noninvasively select candidates for liver biopsy. The treatment of choice remains the changes in lifestyle. Vitamin E and hiazolidinediones have shown evidence in Randomized Clinical Trials. Other medicines will be discussed as well as promising drugs. The present review aims to update the current information of this entity in terms of epidemiology, etiology, diagnosis and treatment(AU)


Subject(s)
Humans , Metabolic Syndrome/physiopathology , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/drug therapy , Internal Medicine , Liver Diseases , Metabolic Diseases
14.
São Paulo; s.n; 2014. [93] p. ilus, tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-870791

ABSTRACT

Introdução: Existem poucas estratégias de intervenção medicamentosa que se mostraram eficazes na doença hepática gordurosa não alcoólica (DHGNA). Os ácidos graxos poliinsaturados (AGPI) Ômega-3 parecem ser eficazes no tratamento da esteatose hepática de modelos experimentais, mas poucos estudos randomizados em humanos foram realizados. O objetivo deste estudo foi avaliar prospectivamente a eficácia de AGPI Ômega-3 provenientes do óleo de linhaça e peixe na esteatohepatite não alcoólica (pacientes com EHNA). Métodos: Sessenta pacientes com biópsia confirmando EHNA foram incluídos no estudo duplo cego, randomizado, placebo controlado. Os pacientes foram randomizados em dois grupos. Grupo Ômega-3 (n = 32) recebeu três cápsulas contendo no total 945 mg de AGPI Ômega-3 (63% ácido alfa linolênico (ALA), 21% ácido eicosapentaenóico (EPA) e 16% do ácido docosahexaenóico (DHA)) e Grupo Placebo (n = 28) recebeu três cápsulas contendo óleo mineral. A intervenção foi realizada por seis meses, quando os pacientes foram novamente submetidos à biópsia hepática. O desfecho primário foi a mudança histológica hepática de acordo com o escore de atividade EHNA (NAS) no início (pré intervenção) e seis meses (após intervenção). Desfecho secundário compreendeu análise das aminotransferases séricas, perfil lipídico e glicemia em jejum, parâmetros antropométricos e nível sérico de IL6 em 0, 3 e 6 meses e dosagem de Ômega-3 plasmático, como prova de tratamento, em 0 e 6 meses. Resultados: Dos 60 pacientes avaliados, 10 não terminaram o estudo (5 no grupo Ômega-3, e 5 no grupo placebo). Analisando os resultados primários, a atividade NAS melhorou ou se manteve estável em 78,26% dos pacientes do grupo placebo e em 55,56% do grupo Ômega-3, sem diferença significativa entre os grupos (p = 0,978), a inflamação lobular reduziu ou se manteve estável em 91,3% no grupo de placebo e em 66,67% no grupo Ômega-3, também sem diferença entre os grupos (p = 0,994). Ômega-3 não...


Introduction: There is a limited number of effective drug treatments available for the treatment of nonalcoholic steatohepatitis (NASH). Polyunsaturaturated fatty acid (PUFAs) Omega 3 seems to be effective in treating hepatic steatosis in experimental animal models, however there is a limited number of humans randomized studies available in the literature. The purpose of the present study is to prospectively evaluate the treatment efficacy of the PUFAs Omega 3 from flaxseed and fish in patients with NASH disease. Methods: A total of sixty biopsy confirmed NASH patients were included in a double blind, randomized, placebo controlled study. They were randomized into two groups: Omega 3 group (n = 32) where patients received a total of 945mg of PUFAs Omega 3 and Placebo group (n = 28) where patients received only mineral oil. After a 6 month treatment all patients underwent a new liver biopsy. Primary goal was to evaluate and compare liver histologic changes, according to Nonalcoholic fatty liver disease (NAFLD) activity score (NAS), between pre and post treatment biopsies. Secondary goal was to evaluate serum transaminases, lipid profile and serum non fasting glucose, anthropometric parameters and serum IL6 at 0, 3 and 6 month treatment. A serum Omega 3 dosage was performed at 0 and 6 month as treatment proof. Results: A total of 50 patients finished the study, 25 from each original group. NAS score improved or was unaltered in 78.26% of the placebo group and in 55.56% of the Omega 3 group (p = 0,978). Lobular liver inflammation was reduced or unaltered in 91.3% and in 66.67% respectively of the placebo and Omega 3 groups (p = 0,994). Omega 3 alone was not able to reduce liver steatosis, hepatocelular balonization or fibrosis. Biochemical analysis revealed reduction on serum triglycerides after 3 month treatment for the Omega 3 group patients, when compared to placebo (p=0,011). Serum transaminases, total cholesterol and fractions, non fasting...


Subject(s)
Humans , Male , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , /therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Double-Blind Method , Evaluation of the Efficacy-Effectiveness of Interventions
15.
Article in Korean | WPRIM | ID: wpr-113903

ABSTRACT

BACKGROUND/AIMS: Chronic hepatocellular damage is closely associated with hepatic fibrosis and fatal complication in most liver diseases. The aim of this study is to compare the efficacy and safety of biphenyl dimethyl dicarboxylate (DDB) and ursodeoxycholic acid (UDCA) in patients with abnormal ALT. METHODS: One-hundred thirty-five patients with elevated ALT were randomized to receive either 750 mg/day of DDB or 300 mg/day of UDCA for 24 weeks in 4 referral hospitals. Ninety-three (69%) patients had non-alcoholic steatohepatitits, 27 (20%) had alcoholic hepatitis, and 15 (11%) had chronic hepatitis. The primary end point was the rate of ALT normalization at week 24. The secondary endpoints were changes in AST, liver stiffness, and the incidence of adverse events. RESULTS: A total of 101 patients completed 24 weeks of therapy. ALT normalization at week 24 was observed in 44 (80.0%) patients in DDB group and 16 (34.8%) in UDCA group (p<0.001). Higher mean reduction of ALT levels from baseline to 24 weeks was seen in DDB group compared with UDCA group (-70.0% vs. -35.9%, p<0.001). Normalization of AST level (p=0.53) and change in the liver stiffness (p=0.703) were not significantly different between the two groups. Severe adverse drug reaction occurred in 1 patient in DDB group but the subject continued therapy during the study period. CONCLUSIONS: DDB was not inferior to UDCA for normalizing ALT level. Furthermore it was safe and well tolerated by patients with abnormal ALT.


Subject(s)
Adolescent , Adult , Aged , Alanine Transaminase/blood , Cholagogues and Choleretics/therapeutic use , Dioxoles/therapeutic use , Double-Blind Method , Drug Administration Schedule , Female , Follow-Up Studies , Hepatitis, Alcoholic/drug therapy , Hepatitis, Chronic/drug therapy , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/drug therapy , Tertiary Care Centers , Treatment Outcome , Ursodeoxycholic Acid/therapeutic use , Young Adult
16.
Article in English | WPRIM | ID: wpr-126670

ABSTRACT

Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen alpha1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor alpha showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.


Subject(s)
Animals , Cholagogues and Choleretics/pharmacology , Diet, High-Fat/adverse effects , Drug Synergism , Fatty Acids, Omega-3/pharmacology , Fibrosis/drug therapy , Inflammation/drug therapy , Liver/drug effects , Male , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/drug therapy , Ursodeoxycholic Acid/pharmacology
17.
Rev. paul. pediatr ; 31(4): 523-530, dez. 2013. graf
Article in English | LILACS | ID: lil-698035

ABSTRACT

OBJECTIVE: To review the literature on the importance of antioxidant vitamins, analyzed in the context of dietary intake, its plasma levels, and its current use as a supplementation treatment in obese children and adolescents with nonalcoholic fatty liver disease. DATA SOURCES: The articles were identified in Lilacs, Ibecs, SciELO, PubMed/Medline, and Scopus databases. To conduct the survey, the "fatty liver" descriptor was associated to the following words: "children", "antioxidants" and "vitamins". The search was limited to articles written in Portuguese, Spanish and English, with publication date until December, 2012. DATA SYNTHESIS: Six studies were selected. The survey revealed a low dietary intake and low antioxidant vitamins serum levels in this population. The changes in lifestyle, with adequate dietary intake of vitamins, and the increase in physical activity were associated with a significant improvement in liver histology and in laboratory tests. Vitamin supplementation also improved the disease progression markers, as the alanine aminotransferase serum levels and the histological characteristics of lobular inflammation and hepatocellular damage. However, these improvements were not statistically significant in all studies. CONCLUSIONS: There is insufficient evidence to recommend or to refute antioxidant supplementation in patients with simple steatosis or steatohepatitis. The changes in lifestyle seem to be, at the present time, the more advisable therapy. .


OBJETIVO: Revisar la literatura sobre la importancia de las vitaminas antioxidantes, analizadas bajo el contexto del consumo dietético, sus respectivos niveles plasmáticos y su actual utilización como tratamiento de suplementación en niños y adolescentes obesos con enfermedad hepática grasosa no alcohólica. FUENTES DE DATOS: Se identificaron los artículos en las bases de datos Lilacs, Ibecs, SciELO, PubMed/MedLine y Scopus. Para realizar la investigación, se utilizó el descriptor "hígado grasoso", asociado a los términos "niño", "antioxidantes" y "vitaminas". La búsqueda se limitó a los artículos en portugués, español e inglés, con fecha límite de publicación hasta diciembre de 2012. SÍNTESIS DE LOS DATOS: Se seleccionaron seis estudios. La investigación reveló baja ingestión dietética y bajos niveles de concentración sérica de vitaminas antioxidantes en la población estudiada. El cambio en los hábitos de vida, con adecuación del consumo dietético de vitaminas y aumento de la actividad física, se asoció a la mejora significativa en la histología hepática y en los exámenes laboratoriales. La suplementación vitamínica también mejoró los marcadores de progresión de la enfermedad, como los niveles séricos de alanina aminotransferasa y las características histológicas de inflamación lobular y lesión hepatocelular. Sin embargo, esas mejorías no fueron estadísticamente significativas en todos los estudios. CONCLUSIONES: No hay evidencias suficientes para recomendar o rechazar la suplementación con antioxidantes en pacientes con esteatosis simple o esteato-hepatitis. El cambio en el estilo de vida parece ser, en el momento, la terapéutica más aconsejable. .


OBJETIVO: Revisar a literatura sobre a importância das vitaminas antioxidantes, analisadas sob o contexto do consumo dietético, seus respectivos níveis plasmáticos e sua atual utilização como tratamento de suplementação em crianças e adolescentes obesos com doença hepática gordurosa não alcoólica. FONTES DE DADOS: Identificaram-se os artigos nas bases de dados Lilacs, Ibecs, SciELO, PubMed/MedLine e Scopus. Para realizar a pesquisa, utilizou-se o descritor "fígado gorduroso", associado aos termos "crianças", "antioxidantes" e "vitaminas". A busca limitou-se aos artigos em português, espanhol e inglês, com data limite de publicação até dezembro de 2012. SÍNTESE DOS DADOS: Selecionaram-se seis estudos. A pesquisa revelou baixa ingestão dietética e baixos níveis de concentração sérica de vitaminas antioxidantes na população estudada. A mudança nos hábitos de vida, com adequação do consumo dietético de vitaminas e aumento da atividade física, associou-se à melhora significativa na histologia hepática e nos exames laboratoriais. A suplementação vitamínica também melhorou os marcadores de progressão da doença, como os níveis séricos de alanina aminotransferase e as características histológicas de inflamação lobular e lesão hepatocelular. Contudo, essas melhorias não foram estatisticamente significativas em todos os estudos. CONCLUSÕES: Não há evidências suficientes para recomendar ou refutar a suplementação com antioxidantes em pacientes com esteatose simples ou esteato-hepatite. A mudança no estilo de vida parece ser, no momento, a terapêutica mais aconselhável. .


Subject(s)
Adolescent , Child , Humans , Antioxidants/therapeutic use , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/drug therapy , Obesity/complications , Obesity/drug therapy , Vitamins/therapeutic use
18.
Braz. j. med. biol. res ; 46(3): 270-277, 15/mar. 2013. tab, graf
Article in English | LILACS | ID: lil-670907

ABSTRACT

Our previous study has shown that reduced insulin resistance (IR) was one of the possible mechanisms for the therapeutic effect of silibinin on non-alcoholic fatty liver disease (NAFLD) in rats. In the present study, we investigated the pathways of silibinin in regulating hepatic glucose production and IR amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD + silibinin group (high-fat diet + 0.5 mg kg-1·day-1 silibinin, starting at the beginning of the protocol). Both subcutaneous and visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR), intraperitoneal glucose tolerance test and insulin tolerance test (ITT) were performed. The expression of adipose triglyceride lipase (ATGL) and of genes associated with hepatic gluconeogenesis was evaluated. Silibinin intervention significantly protected liver function, down-regulated serum fat, and improved IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity, enhancement of lipolysis and inhibition of gluconeogenesis might be the underlying mechanisms.


Subject(s)
Animals , Male , Antioxidants/pharmacology , Insulin Resistance/physiology , Liver/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Silymarin/pharmacology , Glucose Tolerance Test , Homeostasis , Lipid Metabolism/drug effects , Liver/metabolism , Liver/pathology , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/physiopathology , Rats, Sprague-Dawley , Time Factors
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