Jaboticaba (Myrciaria cauliflora) Peel Supplementation Prevents Hepatic Steatosis Through Hypolipidemic Effects and Cholesterol Metabolism Modulation in Diet-Induced Nonalcoholic Fatty Liver Disease Rat Model.

Jaboticaba (Myrciaria cauliflora), a Brazilian fruit, is a good source of dietary fiber and phenolic compounds, which are concentrated mainly in the peel. These compounds have been considered promising in prevention and treatment of hypercholesterolemia and hepatic steatosis. In this study, we investigated the effects of 4% jaboticaba peel powder (JPP) supplementation on cholesterol metabolism and hepatic steatosis in livers of rats fed a high-fat (HF) diet. The rats were fed a standard AIN-93M (control) diet or an HF diet containing 32% lard and 1% cholesterol, both with and without 4% JPP. The M. cauliflora peel composition revealed a low-lipid high-fiber content and phenolic compounds. The phenolic compounds in JPP, tentatively identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS/MS) analysis, were confirmed to contain phenolic acids, flavonoids, and anthocyanins. Moreover, JPP presented significant antioxidant activity in vitro and was not cytotoxic to HepG2 cells, as determined by the lactate dehydrogenase (LDH) assay. After 6 weeks of treatment, our results showed that JPP supplementation increased lipid excretion in feces, reduced serum levels of total cholesterol and nonhigh-density lipoprotein cholesterol, decreased serum aspartate aminotransferase (AST) activity, and attenuated hepatic steatosis severity in rats fed the HF diet. Furthermore, JPP treatment downregulated expression of ACAT-1, LXR-α, CYP7A1, and ABCG5 genes. Therefore, jaboticaba peel may represent a viable dietary strategy to prevent nonalcoholic fatty liver disease as the JPP treatment alleviated hepatic steatosis through improvement of serum lipid profiles and modulation of mRNA expression of genes involved in cholesterol metabolism.

Silymarin Attenuates Hepatic and Pancreatic Redox Imbalance Independent of Glycemic Regulation in the Alloxan-induced Diabetic Rat Model.

OBJECTIVE: To evaluate the efficiency of silymarin (SMN) in modulating metabolic parameters and redox status in rats with type 1 diabetes mellitus (T1DM). METHODS: Diabetes was induced by intraperitoneal injection of alloxan. The diabetic rats were administered with SMN at doses of 50 and 100 mg/kg body weight/d for 30 consecutive days. The rats were divided into the following four groups: vehicle control, diabetic (alloxan-treated), DS50 (alloxan + 50 mg/kg body weight/d of SMN), and DS100 (alloxan + 100 mg/kg body weight/d of SMN) groups. The bodyweight and food and water intake were evaluated. After 30 d, the animals were euthanized and the blood was collected for measuring the serum levels of glucose, triacylglycerol (TAG), urea, and creatinine. The liver and pancreas were collected for measuring the activities of superoxide dismutase (SOD) and catalase (CAT), and the levels of carbonylated protein (PC). The pancreas sample was also used for histological analysis. RESULTS: SMN reduced hepatic ( P < 0.001) and pancreatic ( P < 0.001) protein damage and creatinine levels ( P = 0.0141) in addition to decreasing food ( P < 0.001) and water intake ( P < 0.001). However, treatment with SMN did not improve beta-cell function or decrease blood glucose levels in diabetic rats. CONCLUSION: SMN improved polyphagia and polydipsia, renal function, and protected the liver and pancreas against protein damage without affecting hyperglycemia in diabetic animals.

Açai improves non-alcoholic fatty liver disease (NAFLD) induced by fructose.

INTRODUCTION: the excessive consumption of fructose can cause liver damage, characteristic of non-alcoholic fatty liver disease (NAFLD) associated with changes in lipid metabolism and antioxidant defenses. Açai, the fruit of Euterpe oleraceaMart., has demonstrated numerous biological activities, including anti-inflammatory, antioxidant, and lipid metabolism modulating action. OBJECTIVE: we evaluated the benefits of açai supplementation on liver damage caused by replacing starch with fructose in rats. METHODS: thirty male Fischerrats were divided into two groups, the control group (C, 10 animals), which consumed a standard diet (AIN-93M), and the fructose (F, 20 animals) group, which consumed a diet containing 60% of fructose. After eight weeks, 10 animals from the fructose group received 2% of lyophilized açai, and were called the açai fructose group (FA). The animals were fed ad libitumwith these diets for another ten weeks. Serum, hepatic and fecal lipid profile, antioxidant enzymes and carbonylated protein were assessed and histopathological characterization of the liver was performed. RESULTS: açai promoted the reduction of ALT activity in relation to the fructose group (F), reduced alkaline phosphatase to a level similar to that of the control group (C) in relation to the fructose group (F), and reduced catalase activity. The fruit also increased the ratio of total/oxidized glutathione (GSH/GSSG) and reduced the degree of macrovesicular steatosis and the number of inflammatory cells. CONCLUSION: the replacement of starch by fructose during this period was effective in promoting NAFLD. Açai showed attenuating effects on some markers of hepatic steatosis and inflammation.

Açai improves non-alcoholic fatty liver disease (NAFLD) induced by fructose / El açai mejora la enfermedad de hígado graso no alcohólico (NAFLD) inducida por la fructosa

Introduction: the excessive consumption of fructose can cause liver damage, characteristic of non-alcoholic fatty liver disease (NAFLD) associated with changes in lipid metabolism and antioxidant defenses. Açai, the fruit of Euterpe oleracea Mart., has demonstrated numerous biological activities, including anti-inflammatory, antioxidant, and lipid metabolism modulating action. Objective: we evaluated the benefits of açai supplementation on liver damage caused by replacing starch with fructose in rats. Methods: thirty male Fischer rats were divided into two groups, the control group (C, 10 animals), which consumed a standard diet (AIN-93M), and the fructose (F, 20 animals) group, which consumed a diet containing 60% of fructose. After eight weeks, 10 animals from the fructose group received 2% of lyophilized açai, and were called the açai fructose group (FA). The animals were fed ad libitum with these diets for another ten weeks. Serum, hepatic and fecal lipid profile, antioxidant enzymes and carbonylated protein were assessed and histopathological characterization of the liver was performed. Results: açai promoted the reduction of ALT activity in relation to the fructose group (F), reduced alkaline phosphatase to a level similar to that of the control group (C) in relation to the fructose group (F), and reduced catalase activity. The fruit also increased the ratio of total/oxidized glutathione (GSH/GSSG) and reduced the degree of macrovesicular steatosis and the number of inflammatory cells. Conclusion: the replacement of starch by fructose during this period was effective in promoting NAFLD. Açai showed attenuating effects on some markers of hepatic steatosis and inflammation

Introducción: el consumo excesivo de fructosa puede causar daño hepático, característico de la enfermedad hepática grasa no alcohólica (EHGNA), asociada con cambios en el metabolismo de los lípidos y defensas antioxidantes. El açai, fruto del Euterpe oleracea Mart., ha demostrado desempeñar numerosas actividades biológicas, incluidas acciones antiinflamatorias, antioxidantes y moduladoras del metabolismo lipídico. Objetivo: se evaluaron los beneficios de la suplementación con açai en el daño hepático causado por la sustitución del almidón por fructosa en ratas. Métodos: se distribuyeron 30 ratas Fischer macho en dos grupos: 10 ratas en el grupo control (C), que consumía una dieta estándar (AIN-93M), y 20 ratas en el grupo fructosa (F), que consumía una dieta que contenía un 60% de fructosa. Después de ocho semanas, diez animales del grupo fructosa recibieron un 2% de açai liofilizado, por lo que pasaron a integrar el grupo açai fructosa (FA). Los animales fueron alimentados ad libitum con estas dietas durante otras diez semanas. Se analizaron el perfil lipídico hepático y fecal, las enzimas antioxidantes y la proteína carbonilada, y se realizó la caracterización histopatológica del hígado. Resultados: el açai promovió la reducción de la actividad de ALT en relación al grupo de fructosa (F) y la reducción de la fosfatasa alcalina a niveles similares a los hallados en el grupo control (C) en relación con el grupo de fructosa (F). El fruto también aumentó la proporción de glutatión total/oxidado (GSH/GSSG) y redujo el grado de esteatosis macrovesicular y el número de células inflamatorias. Conclusión: la sustitución de almidón por fructosa durante este periodo fue eficaz en la promoción de NAFLD. El açai mostró efectos atenuantes en algunos marcadores de esteatosis hepática y de inflamación

Myocarditis in different experimental models infected by Trypanosoma cruzi is correlated with the production of IgG1 isotype.

This study was designed to verify the relationship between IgG antibodies isotypes and myocarditis in Trypanosoma cruzi infection using mice and dogs infected with different T. cruzi strains. The animals were infected with benznidazole-susceptible Berenice-78 and benznidazole-resistant AAS and VL-10 strains. The IgG subtypes were measured in serum samples from dogs (IgG, IgG1, and IgG2) and mice (IgG, IgG1, IgG2a, and IgG2b). The infection of dogs with VL-10 strain induced the highest levels of heart inflammation while intermediate and lower levels were detected with Berenice-78 and AAS strains, respectively. Similar results were found in mice infected with VL-10, but not in those infected with AAS or Berenice-78 strains. The AAS strain induced higher levels of heart inflammation in mice, while Berenice-78 strain was not able to induce it. Correlation analysis between myocarditis and antibody reactivity index revealed very interesting results, mainly for IgG and IgG1, the latter being the most exciting. High IgG1 showed a significant correlation with myocarditis in both experimental models, being more significant in dogs (r=0.94, p<0.0001) than in mice (r=0.58, p=0.047). Overall, our data suggest that IgG1 could be a good marker to demonstrate myocarditis intensity in Chagas disease.

Hypercholesterolemic diet induces hepatic steatosis and alterations in mRNA expression of NADPH oxidase in rat livers.

OBJECTIVE: This study aimed to determine whether a hypercholesterolemic diet induces hepatic steatosis, alterations in mRNA expression of NADPH oxidase subunits, and antioxidant defenses. MATERIALS AND METHODS: Fischer rats were divided into two groups of eight animals according to the treatment, control (C) and hypercholesterolemic diet (H). Those in group C were fed a standard diet (AIN-93M), and those of the group H were fed a hypercholesterolemic diet (25% soybean oil and 1% cholesterol). RESULTS: The hypercholesterolemic diet did not affect body weight, but resulted in the accumulation of lipids in the liver, increased serum activities of aminotransferases and cholesterol levels. Biomarker of lipid peroxidation (TBARS) and mRNA expression of NADPH oxidase subunits p22(phox) and p47(phox) were increased in the liver of animals in group H. Besides, the activity and expression of antioxidant enzymes were altered. CONCLUSION: The results show increased mRNA expression of NADPH oxidase subunits and changes in antioxidant enzyme activities in diet-induced hepatic steatosis.

Hypercholesterolemic diet induces hepatic steatosis and alterations in mRNA expression of NADPH oxidase in rat livers / Dieta hipercolesterolemiante induz esteatose hepática e alterações na expressão de mRNA da NADPH oxidase em fígados de ratos

Objective : This study aimed to determine whether a hypercholesterolemic diet induces hepatic steatosis, alterations in mRNA expression of NADPH oxidase subunits, and antioxidant defenses.Materials and methods : Fischer rats were divided into two groups of eight animals according to the treatment, control (C) and hypercholesterolemic diet (H). Those in group C were fed a standard diet (AIN-93M), and those of the group H were fed a hypercholesterolemic diet (25% soybean oil and 1% cholesterol).Results : The hypercholesterolemic diet did not affect body weight, but resulted in the accumulation of lipids in the liver, increased serum activities of aminotransferases and cholesterol levels. Biomarker of lipid peroxidation (TBARS) and mRNA expression of NADPH oxidase subunits p22phox and p47phox were increased in the liver of animals in group H. Besides, the activity and expression of antioxidant enzymes were altered.Conclusion : The results show increased mRNA expression of NADPH oxidase subunits and changes in antioxidant enzyme activities in diet-induced hepatic steatosis. Arq Bras Endocrinol Metab. 2014;58(3):251-9.

Objetivo Determinar se uma dieta hipercolesterolemiante induz esteatose hepática, alterações na expressão de mRNA da NADPH oxidase e nas defesas antioxidantes.Materiais e métodos : Ratas Fischer foram divididas em dois grupos de oito animais de acordo com o tratamento recebido, controle (C) e hipercolesterolêmico (H). Aquelas do grupo C foram alimentadas com dieta padrão (AIN-93M) e as do grupo H foram alimentadas com dieta hipercolesterolemiante (25% de óleo de soja e 1% de colesterol). As dietas foram oferecidas por oito semanas.Resultados : O grupo H apresentou acúmulo de lipídios no fígado, aumento das atividades de ALT e AST e da concentração de colesterol no soro comparado ao grupo C. O marcador da peroxidação lipídica (TBARS) e os níveis de mRNA das subunidades p47phox da NADPH-oxidase e p22phox foram aumentados no fígado de animais do grupo H, além de alteração da atividade e expressão de enzimas antioxidantes.Conclusão : Os resultados mostram um aumento na expressão de subunidades da NADPH oxidase e alterações na atividade das enzimas antioxidantes na esteatose hepática induzida por dieta hipercolesterolemiante. Arq Bras Endocrinol Metab. 2014;58(3):251-9.

Real-time PCR strategy for parasite quantification in blood and tissue samples of experimental Trypanosoma cruzi infection.

The lack of an accurate diagnosis has been a serious obstacle to the advancement of the anti-Trypanosoma cruzi chemotherapy and long-term infection can result in different health risks to human. PCRs are alternative methods, more sensitive than conventional parasitological techniques, which due to their low sensitivities are considered unsuitable for these purposes. The aim of this study was to investigate a sensitive diagnostic strategy to quantify blood and cardiac tissues parasites based on real-time PCR tools during acute and chronic phases of murine Chagas disease, as well as to monitor the evolution of infection in those mice under specific treatment. In parallel, fresh blood examination, immunological analysis and quantification of cardiac inflammation were also performed to confront and improve real-time PCR data. Similar profiles of parasitemia curves were observed in both quantification techniques during the acute phase of the infection. In contrast, parasites could be quantified only by real-time PCR at 60 and 120 days of infection. In cardiac tissue, real-time PCR detected T. cruzi DNA in 100% of infected mice, and using this tool a significant Pearson correlation between parasite load in peripheral blood and in cardiac tissue during acute and chronic phases was observed. Levels of serum CCL2, CCL5 and nitric oxide were coincident with parasite load but focal and diffuse mononuclear infiltrates was observed, even with significant (p<0.05) reduction of parasitism after 60 days of infection. Later, this methodology was used to monitor the evolution of infection in animals treated with itraconazole (Itz). Itz-treatment induced a reduction of parasite load in both blood and cardiac muscle at the treatment period, but after the end of chemotherapy an increase of parasitism was detected. Interestingly, inflammatory mediators levels and heart inflammation intensity had similar evolution to the parasite load, in the group of animals treated. Taken together, our data show that real-time PCR strategy used was suitable for studies of murine T. cruzi infection and may prove useful in investigations involving experimental chemotherapy of the disease and the benefits of treatment in relation to parasitism and inflammatory response.

[Effect of streptozotocin on the glycemic and lipid profiles and oxidative stress in hamsters]. / Efeito da estreptozotocina sobre os perfis glicêmico e lipídico e o estresse oxidativo em hamsters.

OBJECTIVE: This study evaluated the effects of streptozotocin on glycemic and lipid profiles and oxidative stress status in hamsters. MATERIALS AND METHODS: Male Golden Syrian hamsters were divided in diabetic group (D) which received a streptozotocin single injection (STZ - 50 mg/kg), and control group (C) which received a single injection of the vehicle citrate buffer. Animals were euthanized after 10 days of experiment and blood, liver and kidneys were collected. RESULTS: The diabetic group had higher levels of glucose, triacylglycerols and cholesterol in serum and thiobarbituric acid reactive substances (TBARS) concentration increased in the liver and kidneys. Diabetes induced a significant increase in glutathione concentration in the liver and decreased paraoxonase and superoxide dismutase activities. CONCLUSION: Hamsters provide a novel animal model for diabetes mellitus and oxidative stress, similar to the human syndrome, which may be suitable for the testing of antidiabetic compounds.

Efeito da estreptozotocina sobre os perfis glicêmico e lipídico e o estresse oxidativo em hamsters / Effect of streptozotocin on the glycemic and lipid profiles and oxidative stress in hamsters

OBJETIVO: Este estudo avaliou os efeitos da estreptozotocina nos perfis glicêmico e lipídico e marcadores de estresse oxidativo em hamsteres. MATERIAIS E MÉTODOS: Hamsteres machos Golden Syrian foram divididos em dois grupos: grupo diabético (D), que recebeu uma única injeção de estreptozotocina (STZ - 50 mg/kg), e grupo controle (C), que recebeu injeção de tampão citrato. Os animais foram eutanasiados após 10 dias de experimento e o sangue, o fígado e rins foram coletados. RESULTADOS: O grupo diabético apresentou níveis maiores de glicose, triacilgliceróis e colesterol séricos e maior concentração de substâncias reativas ao ácido tiobarbitúrico (TBARs) no fígado e nos rins. Também apresentou significativo aumento da concentração de glutationa no fígado e menores atividades da paraoxonase e do superóxido dismutase. CONCLUSÃO: Hamsteres fornecem um bom modelo para o diabetes melito do tipo I e estresse oxidativo, similar ao da síndrome humana, e poderão ser adequados para a análise de compostos antidiabéticos.

OBJECTIVE: This study evaluated the effects of streptozotocin on glycemic and lipid profiles and oxidative stress status in hamsters. MATERIALS AND METHODS: Male Golden Syrian hamsters were divided in diabetic group (D) which received a streptozotocin single injection (STZ - 50 mg/kg), and control group (C) which received a single injection of the vehicle citrate buffer. Animals were euthanized after 10 days of experiment and blood, liver and kidneys were collected. RESULTS: The diabetic group had higher levels of glucose, triacylglycerols and cholesterol in serum and thiobarbituric acid reactive substances (TBARS) concentration increased in the liver and kidneys. Diabetes induced a significant increase in glutathione concentration in the liver and decreased paraoxonase and superoxide dismutase activities. CONCLUSION: Hamsters provide a novel animal model for diabetes mellitus and oxidative stress, similar to the human syndrome, which may be suitable for the testing of antidiabetic compounds.