Potential of piperine for neuroprotection in sepsis-associated encephalopathy.

AIMS: Sepsis-associated encephalopathy (SAE) is a common complication that increases mortality and leads to long-term cognitive impairment in sepsis survivors. However, no specific or effective therapy has been identified for this complication. Piperine is an alkaloid known for its anti-inflammatory, antioxidant, and neuroprotective properties, which are important characteristics for treatment of SAE. The objective of this study was to evaluate the neuroprotective effect of piperine on SAE in C57BL/6 mice that underwent cecum ligation and perforation surgery (CLP). MAIN METHODS: C57BL/6 male mice were randomly assigned to groups that underwent SHAM surgery or CLP. Mice in the CLP group were treated with piperine at doses of 20 or 40 mg/kg for short- (5 days) or long-term (10 days) periods after CLP. KEY FINDINGS: Our results revealed that untreated septic animals exhibited increased concentrations of IL-6, TNF, VEGF, MMP-9, TBARS, and NLRP3, and decreased levels of BDNF, sulfhydryl groups, and catalase in the short term. Additionally, the levels of carbonylated proteins and degenerated neuronal cells were increased at both time points. Furthermore, short-term and visuospatial memories were impaired. Piperine treatment reduced MMP-9 activity in the short term and decreased the levels of carbonylated proteins and degenerated neuronal cells in the long term. It also lowered IL-6 and TBARS levels at both time points evaluated. Moreover, piperine increased short-term catalase and long-term BDNF factor levels and improved memory at both time points. SIGNIFICANCE: In conclusion, our data demonstrate that piperine exerts a neuroprotective effect on SAE in animals that have undergone CLP.

High-fat diet increases mortality and intensifies immunometabolic changes in septic mice.

Immunometabolic changes in the liver and white adipose tissue caused by high-fat (HF) diet intake may worse metabolic adaptation and protection against pathogens in sepsis. We investigate the effect of chronic HF diet (15 weeks) on mortality and immunometabolic responses in female mice after sepsis induced by cecum ligation and perforation (CLP). At week 14, animals were divided into four groups: sham C diet, sepsis C diet (C-Sp), sham HF diet (HF-Sh) and sepsis HF diet (HF-Sp). The surviving animals were euthanized on the 7th day. The HF diet decreased survival rate (58.3% vs. 76.2% C-Sp group), increased serum cytokine storm (IL-6 [1.41 ×; vs. HF-Sh], IL-1ß [1.37 ×; vs. C-Sp], TNF [1.34 ×; vs. C-Sp and 1.72 ×; vs. HF-Sh], IL-17 [1.44 ×; vs. HF-Sh], IL-10 [1.55 ×; vs. C-Sp and 1.41 ×; HF-Sh]), white adipose tissue inflammation (IL-6 [8.7 ×; vs. C-Sp and 2.4 ×; vs. HF-Sh], TNF [5 ×; vs. C-Sp and 1.7 ×; vs. HF-Sh], IL-17 [1.7 ×; vs. C-Sp], IL-10 [7.4 ×; vs. C-Sp and 1.3 ×; vs. HF-Sh]), and modulated lipid metabolism in septic mice. In the HF-Sp group liver's, we observed hepatomegaly, hydropic degeneration, necrosis, an increase in oxidative stress (reduction of CAT activity [-81.7%; vs. HF-Sh]; increase MDA levels [82.8%; vs. HF-Sh], and hepatic IL-6 [1.9 ×; vs. HF-Sh], and TNF [1.3 × %; vs. HF-Sh]) production. Furthermore, we found a decrease in the total number of inflammatory, mononuclear cells, and in the regenerative processes, and binucleated hepatocytes in a HF-Sp group livers. Our results suggested that the organism under metabolic stress of a HF diet during sepsis may worsen the inflammatory landscape and hepatocellular injury and may harm the liver regenerative process.

EPA/DHA and linseed oil have different effects on liver and adipose tissue in rats fed with a high-fat diet.

The incidence of cardiovascular diseases and metabolic disorders has increased worldwide. Clinical and experimental research has shown that the consumption of ω-3 FAs can be beneficial to metabolism in several ways, as they can act on metabolic pathways. Our objective was to evaluate the effect of treatment with linseed oil, a vegetable oil rich in alpha-linolenic acid, and EPA and DHA in different proportions (3:1 EPA:DHA, and 1:3 EPA:DHA), on the metabolic disorders induced by a high-fat diet (20 % lipids) in rats for 2 weeks, after 18 weeks of consumption of a high-fat diet. In 18 weeks, the high-fat diet increased blood glucose, systolic blood pressure, triglyceride concentration in the liver and adipose tissue, and impaired insulin sensibility without interfering in the weight of the animals. All treatments were effective in reducing the deposition of hepatic type III collagen, the proportion of ω-6/ω-3 in the liver and WAT (white adipose tissue), the proportion of area/number of adipocytes, and the gene expression of the ACC, FAS, and CPT1 enzymes. In addition, treatment with EPA and DHA reduced blood glucose, serum TNF-α concentration, amount of liver fat, degree of microsteatosis and type I collagen deposition in the liver, deposition of type I and III collagen in TA, gene expression of the transcription factor SREBP-1c, and increased hepatic binucleation. EPA in major proportion was more effective in reducing the area of adipocytes, hepatic triglyceride concentration, PPAR-α expression, and WAT fat weight. DHA in a major proportion reduced the concentration of MCP1 in WAT. LO treatment did not have any isolated effects. We concluded that EPA and DHA were more effective in treating metabolic damage than treatment with LO, leading to a more favorable metabolic profile.

Temporal effect of fructose supplementation at different concentrations on hepatic metabolism of Wistar rats.

INTRODUCTION: Introduction: in the last few years important changes have occurred in nutritional patterns. There has been an increase in the consumption of simple carbohydrates such as fructose, which has been associated with numerous metabolic disorders, including hepatic steatosis. Materials and methods: we sought to evaluate the impact of fructose consumption, as diluted in water at different concentrations, for two time periods, on the metabolic parameters of Wistar rats using ANOVA. Results: our data indicate that both time and fructose concentration promote variations in animal body mass, and in food, water, and caloric intake. The time variable influenced the modulation of biochemical parameters such as serum concentrations of glucose and total cholesterol. Both fructose concentration and time of exposure influenced the concentrations of serum triglycerides, creatinine, AST, TNF, and IL-6. When evaluating redox status and oxidative damage markers, we observed that fructose concentration and exposure time had an effect on total glutathione levels, which decreased with an increase in concentration and time. For superoxide dismutase, we evaluated the effects of time and interaction. A significant interaction was observed for TBARS. For carbonylated proteins, exposure time was a fundamental factor in generating an effect. Conclusions: we demonstrated that fructose modulates the parameters of triglycerides and total liver cholesterol, and that time influences the number of hepatocytes. Our data suggest that fructose concentration, exposure time, and an interaction between these two parameters have a significant effect on the metabolic parameters responsible for the development of non-alcoholic fatty liver disease.

INTRODUCCIÓN: Introducción: en los últimos años se han producido cambios importantes en los patrones nutricionales. Ha habido un aumento del consumo de carbohidratos simples como la fructosa, que se ha asociado con numerosos trastornos metabólicos, incluida la esteatosis hepática. Materiales y métodos: buscamos evaluar el impacto del consumo de fructosa, diluida en agua a diferentes concentraciones, durante dos períodos de tiempo sobre los parámetros metabólicos de ratas Wistar, utilizando para ello el ANOVA. Resultados: nuestros datos indican que tanto el tiempo como la concentración de fructosa promueven variaciones en la masa corporal animal y la ingesta de alimentos, agua y calorías. La variable tiempo influyó en la modulación de parámetros bioquímicos tales como las concentraciones séricas de glucosa y colesterol total. Tanto la concentración de fructosa como el tiempo de exposición influyeron en las concentraciones séricas de triglicéridos, creatinina, AST, TNF e IL-6. Al evaluar el estado redox y los marcadores de daño oxidativo, observamos que la concentración de fructosa y el tiempo de exposición tuvieron un efecto sobre los niveles de glutatión total, que disminuyeron al aumentar la concentración y el tiempo. Para la superóxido dismutasa evaluamos los efectos del tiempo y la interacción. Se observó una interacción significativa para TBARS. Para las proteínas carboniladas, el tiempo de exposición fue un factor fundamental para generar algún efecto. Conclusiones: demostramos que la fructosa modula los parámetros de los triglicéridos y el colesterol total del hígado, y que el tiempo influye en el número de hepatocitos. Nuestros datos sugieren que la concentración de fructosa, el tiempo de exposición y cierta interacción entre estos dos parámetros tienen un efecto significativo sobre los parámetros metabólicos responsables del desarrollo de la enfermedad del hígado graso no alcohólico.

Açaí (Euterpe oleracea Martius) Promotes Jejunal Tissue Regeneration by Enhancing Antioxidant Response in 5-Fluorouracil-Induced Mucositis.

Intestinal mucositis (IM) caused by antineoplastic chemotherapy is characterized by an important inflammatory process, which may compromise ongoing treatment. Our study aimed to investigate the effect of Açaí (Euterpe oleracea Martius) on the antioxidant response in BALB/c mice pretreated with Açaí pulp (200 g/kg) for 14 day. A group of animals receiving a single intraperitoneal injection of 5-FU (200 mg/kg) were euthanized on day three (D3) or seven (D7) after administration, the distal jejunum was isolated for the analyses of histology, superoxide dismutase (SOD) and catalase (CAT) enzyme activities, and concentration of total sulfhydryl groups (GSH). Seven days after induction, the intake of Açaí by the IM group almost completely regenerated tissue histology. Notably, SOD activity decreased in the MUC + Açaí group (D3). CAT activity reduced on D3 and D7 in the IM groups and Açaí treatment groups, respectively. No change was observed in the total GSH concentration at the tissue level. Our results demonstrated the protective effect of Açaí pulp components on intestinal damage induced by 5-FU, as well as the ability to control the response to oxidative stress, in order to mobilize defense pathways and promote tissue repair.