Chronic Oral Administration of Aluminum Hydroxide Stimulates Systemic Inflammation and Redox Imbalance in BALB/c Mice.

The present study is aimed at investigating the long-term effects of the aluminum hydroxide administration in the small intestine, lung, liver, and kidney of male BALB/c mice. The mice received via orogastric gavage phosphate buffered or 10 mg/kg aluminum hydroxide 3 times a week for 6 months. Administration of aluminum hydroxide decreased hemoglobin, hematocrit, and erythrocyte. In the blood, kidney and liver function markers were evaluated, and long-term administration of aluminum hydroxide led to an increase in AST levels and a decrease in urea levels. The animals exposed to aluminum showed higher lipid and protein oxidation in all the organs analyzed. In relation to the enzymes involved in antioxidant defense, the lungs showed lower superoxide dismutase (SOD) and catalase activity and a lower reduced and oxidized glutathione (GSH/GSSG) ratio. In the liver, aluminum administration led to a decrease in catalase activity and the GSH/GSSG ratio. Lower catalase activity was observed in the small intestine, as well as in the lungs and liver. In addition to alterations in antioxidant defense, increased levels of the chemokine CCL-2 were observed in the lungs, lower levels of IL-10 in the liver and small intestine, and decreased levels of IL-6 in the intestine of the animals that received aluminum hydroxide for 6 months. Long-term exposure to aluminum promoted steatosis in the liver. In the kidneys, mice treated with aluminum presented a decreased glomerular density than in the naive control group. In the small intestine, exposure caused villi shortening. Our results indicate that long-term oral administration of aluminum hydroxide provokes systemic histological damage, inflammation, and redox imbalance.

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.

The imbalance in the relationship between inflammatory and regulatory cytokines during gestational toxoplasmosis can be harmful to fetuses: A systematic review.

Objective: To evaluate the available information on inflammatory and regulatory plasma mediators in pregnant women (PW) diagnosed with toxoplasmosis. Source: The PubMed, Embase, Scopus, and Lilacs databases were evaluated until October 2022. Study eligibility criteria: This review was carried out following the PRISMA and registered on the PROSPERO platform (CRD42020203951). Studies that reported inflammatory mediators in PW with toxoplasmosis were considered. Evaluation methods: After excluding duplicate articles, two authors independently carried out the process of title and abstract exclusion, and a third resolved disagreements when necessary. The full text was evaluated to detect related articles. The extraction table was built from the following data: Author, year of publication, journal name and impact factors, country, study design, number of gestations and maternal age (years), gestational period, diagnosis of toxoplasmosis, levels of inflammatory markers, laboratory tests, and clinical significance. Methodological quality was assessed using Joanna Briggs Institute tools. Results: Of the 1,024 studies reported, only eight were included. Of the 868 PW included in this review, 20.2% were IgM+/IgG- and 50.8% were IgM-/IgG+ to T. gondii, and 29.0% uninfected. Infected PW presented higher plasma levels ofIL-5, IL-6, IL-8, IL-17, CCL5, and IL-10. Regarding the methodological quality, four studies obtained high quality. Data from this review pointed out the maintenance of the inflammatory pattern during pregnancy with a closely related to the parasite. Conclusion: Immune status in PW defined the course of the T. gondii infection, where the equilibrium between inflammatory and regulatory cytokines mitigated the harmful placenta and fetus effects. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420203951.

Similar Inflammatory Adaptation in Women following 10 Weeks of Two Equalized Resistance Training with Different Muscle Action Duration.

This study is aimed at evaluating the profile of inflammatory markers and components of redox regulation in untrained women after 10 weeks of resistance training using equalized protocols but different muscle action duration (MAD). Twenty-two women underwent progressive resistance training exercising the knee extensor muscles for 10 weeks-3x/week, with 3-5 sets of 6 repetitions at 50% of the 1 repetition maximum strength test (1RM), with a rest of 180 s between the series, following the training protocol (i) 5 s of concentric muscle action for 1 s of eccentric muscle action (5C-1E) and (ii) 1 s of concentric muscle action for 5 s of eccentric muscle action (1C-5E). Quadriceps muscle hypertrophy maximum strength (1RM) and redox regulation/muscle damage/inflammatory markers (CAT, SOD, TBARS, FRAP, CH, LDH, CXCL8, and CCL2) were evaluated. Plasma markers were evaluated before and 30 minutes after the first and last training sessions. A similar gain in hypertrophy and maximum strength was observed in both groups. However, in the 5C-1E, a significant major effect was observed for SOD (F 1.19 = 10.480, p = 0.004) and a significant major time effect, with a reduction in the last training session, was observed for CXCL8 (F 1.37 = 27.440, p < 0.001). In conclusion, similar protocols of resistance training, with different MAD, produced similar inflammatory and adaptive responses to strength training. As the training load is progressive, the maintenance of this inflammatory and redox regulation profile suggests an adaptive response to the proposed strength training.

Quercetin Improves Pulmonary Function and Prevents Emphysema Caused by Exposure to Cigarette Smoke in Male Mice.

Chronic obstructive pulmonary disease (COPD) is the major cause of morbidity and mortality worldwide, and cigarette smoke is a key factor in the development of COPD. Thus, the development of effective therapies to prevent the advancement of COPD has become increasingly essential. We hypothesized that quercetin protects lungs in mice exposed to long-term cigarette smoke. Thirty-five C57BL/6 mice were exposed to cigarette smoke (12 cigarettes per day) for 60 days and pretreated with 10 mg/kg/day of quercetin via orogastric gavage. After the experimental protocol, the animals were euthanized and samples were collected for histopathological, antioxidant defense, oxidative stress and inflammatory analysis. The animals exposed to cigarette smoke showed an increase in respiratory rate and hematological parameters, cell influx into the airways, oxidative damage and inflammatory mediators, besides presenting with alterations in the pulmonary histoarchitecture. The animals receiving 10 mg/kg/day of quercetin that were exposed to cigarette smoke presented a reduction in cellular influx, less oxidative damage, reduction in cytokine levels, improvement in the histological pattern and improvement in pulmonary emphysema compared to the group that was only exposed to cigarette smoke. These results suggest that quercetin may be an agent in preventing pulmonary emphysema induced by cigarette smoke.

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.

Diet Rich in Lard Promotes a Metabolic Environment Favorable to Trypanosoma cruzi Growth.

Background: Trypanosoma cruzi is a protozoan parasite that causes Chagas disease and affects 6-7 million people mainly in Latin America and worldwide. Here, we investigated the effects of hyperlipidic diets, mainly composed of olive oil or lard on experimental T. cruzi infection. C57BL/6 mice were fed two different dietary types in which the main sources of fatty acids were either monounsaturated (olive oil diet) or saturated (lard diet). Methods: After 60 days on the diet, mice were infected with 50 trypomastigote forms of T. cruzi Colombian strain. We evaluated the systemic and tissue parasitism, tissue inflammation, and the redox status of mice after 30 days of infection. Results: Lipid levels in the liver of mice fed with the lard diet increased compared with that of the mice fed with olive oil or normolipidic diets. The lard diet group presented with an increased parasitic load in the heart and adipose tissues following infection as well as an increased expression of Tlr2 and Tlr9 in the heart. However, no changes were seen in the survival rates across the dietary groups. Infected mice receiving all diets presented comparable levels of recruited inflammatory cells at 30 days post-infection but, at this time, we observed lard diet inducing an overproduction of CCL2 in the cardiac tissue and its inhibition in the adipose tissue. T. cruzi infection altered liver antioxidant levels in mice, with the lard diet group demonstrating decreased catalase (CAT) activity compared with that of other dietary groups. Conclusions: Our data demonstrated that T. cruzi growth is more favorable on tissue of mice subjected to the lard diet. Our findings supported our hypothesis of a relationship between the source of dietary lipids and parasite-induced immunopathology.

Genetic polymorphism in IL17RA induces susceptibility to Toxoplasma gondii infection in Brazilian pregnant women.

Congenital toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, an obligate intracellular parasite which can cause fetal death/abortion and can induce damage in the brain and eyes of the infected babies. The environmental and genetic factors associated with T. gondii and the maternal immune response, drive part of the pathogenesis of congenital toxoplasmosis. Thus, in this study, we aimed to investigate the allelic and genotypic frequencies of specific single nucleotide polymorphisms (SNPs) in the IL17A and IL17RA genes, as well as the production of IL-17A, IL-33, and CCL2 in pregnant women, from the State of Rio Grande do Norte, Brazil, further relating these along with the clinical parameters, to the toxoplasmosis infection. Through PCR-RFLP techniques, two SNPs implicated in Th17 immune response, IL17A rs2275913 (G> A) and IL17RA rs4819554 (A> G) modulation were evaluated in pregnant women, either infected or not infected by T. gondii. These women were also evaluated in terms of plasma release of CCL2, IL-33, and IL-17A which relate to hypertension, number of abortions, and ethnic pattern. The results showed that the G-allele of the SNP rs2275913 (IL17A) appeared to be protective in this population, while the rs4819554 (IL17RA) SNP G allele was associated with greater susceptibility to T. gondii infection [ρ value = 0.025; OR = 2.815 (1.118-7.089); CI = 95%]. None of the cytokines had any influence on the analyzed parameters (abortion and hypertension). In conclusion, our data suggest an immunogenic evidence of susceptibility to T. gondii infection driven by the rs4819554 (IL17RA) SNP G allele in Brazilian pregnant women. Further studies are needed to reinforce this trial marker in populations from distinct geographical areas as well as to confirm the protective pattern related to the G-allele of the SNP rs2275913 (IL17A) in pregnant women.

A High-Fat Diet Exacerbates the Course of Experimental Trypanosoma cruzi Infection That Can Be Mitigated by Treatment with Simvastatin.

The protozoan Trypanosoma cruzi is responsible for triggering a damage immune response in the host cardiovascular system. This parasite has a high affinity for host lipoproteins and uses the low-density lipoprotein (LDL) receptor for its invasion. Assuming that the presence of LDL cholesterol in tissues could facilitate T. cruzi proliferation, dietary composition may affect the parasite-host relationship. Therefore, the aim of this study was to evaluate myocarditis in T. cruzi-infected C57BL/6 mice-acute phase-fed a high-fat diet and treated with simvastatin, a lipid-lowering medication. Animals (n = 10) were infected with 5 × 103 cells of the VL-10 strain of T. cruzi and treated or untreated daily with 20 mg/kg simvastatin, starting 24 h after infection and fed with a normolipidic or high-fat diet. Also, uninfected mice, treated or not with simvastatin and fed with normolipidic or high-fat diet, were evaluated as control groups. Analyses to measure the production of chemokine (C-C motif) ligand 2 (CCL2), interferon- (IFN-) γ, interleukin- (IL-) 10, and tumor necrosis factor (TNF); total hepatic lipid dosage; cholesterol; and fractions, as well as histopathological analysis, were performed on day 30 using cardiac and fat tissues. Our results showed that the high-fat diet increased (i) parasite replication, (ii) fat accumulation in the liver, (iii) total cholesterol and LDL levels, and (iv) the host inflammatory state through the production of the cytokine TNF. However, simvastatin only reduced the production of CCL2 but not that of other inflammatory mediators or biochemical parameters. Together, our data suggest that the high-fat diet may have worsened the biochemical parameters of the uninfected and T. cruzi-infected animals, as well as favored the survival of circulating parasites.

Anti-Inflammatory and Antioxidant Properties of Black Mulberry (Morus nigra L.) in a Model of LPS-Induced Sepsis.

Sepsis is a complex disease and is the cause of many deaths worldwide. Sepsis pathogenesis involves a dysregulated inflammatory response with consequent production of inflammatory mediators and reactive species. The production and excessive release of these substances into the systemic circulation trigger various cellular and metabolic alterations that are observed during the disease evolution. Thus, more studies have been carried out to investigate the therapeutic potential of plants such as Morus nigra L., popularly known as black mulberry. Studies have shown that plants belonging to the Morus genus are rich in secondary metabolites such as flavonoids which are associated with important biological activities as antioxidant and anti-inflammatory actions. Based on this context, the objective of our study was to evaluate the anti-inflammatory and antioxidant properties of Morus nigra L. in a sepsis model induced by LPS. Male C57BL/6 mice were distributed in four groups: control, sepsis, sepsis treated with leaf extract of mulberry, and sepsis treated with mulberry pulp. The animals were treated with 100 µL of their respective treatments for twenty-one days. Sepsis was induced at the 21st day with lipopolysaccharide (LPS) by intraperitoneal injection. The animals were euthanized 24 hours after receiving the LPS injection. The data obtained were analyzed in GraphPad Prism 6.0 software. Our results showed that treatment with either extract significantly decreased the number of leukocytes in the bronchoalveolar lavage fluid and serum levels of TNF in septic animals. Regarding the redox status, the treatments significantly decreased the antioxidant activity of the enzyme glutathione peroxidase. Regarding metalloproteinase type 2, it was observed that the treatment with black mulberry pulp was able to significantly reduce the activity of this enzyme concerning the sepsis group. Finally, these results together promoted an increase in the animal's survival that received the black mulberry leaf or pulp extract.

Strength Training Session Induces Important Changes on Physiological, Immunological, and Inflammatory Biomarkers.

Strength exercise is a strategy applied in sports and physical training processes. It may induce skeletal muscle hypertrophy. The hypertrophy is dependent on the eccentric muscle actions and on the inflammatory response. Here, we evaluate the physiological, immunological, and inflammatory responses induced by a session of strength training with a focus on predominance of the eccentric muscle actions. Twenty volunteers were separated into two groups: the untrained group (UTG) and the trained group (TG). Both groups hold 4 sets of leg press, knee extensor, and leg curl at 65% of personal one-repetition maximum (1RM), 90 s of recovery, and 2″conc/3″eccen of duration of execution in each repetition. Blood samples were collected immediately before and after, 2 hours after, and 24 h after the end of the exercise session. The single session of strength training elevated the heart rate (HR), rating of perceived exertion (RPE), visual analog scale (VAS), and lactate blood level in UTG and TG. Creatine kinase (CK) levels were higher at 2 and 24 h after the end of the exercise in UTG and, in TG, only at 24 h. The number of white blood cells (WBC) and neutrophils increased in UTG and TG, post and 2 h after exercise. Lymphocytes increased postexercise but reduced 2 h after exercise in both groups, while the number of monocytes increased only immediately after the exercise session in UTG and TG. The strength training session elevated the levels of apelin and fatty acid-binding proteins-3 (FABP3) in both groups and brain-derived neurotrophic factor (BDNF) in TG. The single exercise session was capable of inducing elevated HR, RPE, lactate level, and CK levels. This protocol changed the count/total number of circulating immune cells in both groups (UTG and TG) and also increased the level of plasmatic apelin, BDNF, and FLTS1 only in TG and FABP3 myokines in both groups.

[The Brazilian School Nutrition Program from the standpoint of students attending state schools in Minas Gerais, Brazil]. / O Programa Nacional de Alimentação Escolar sob a ótica dos alunos da rede estadual de ensino de Minas Gerais, Brasil.

The scope of this article is to analyze the Brazilian School Nutrition Program from the standpoint of students attending state schools in Minas Gerais. It is a qualitative and quantitative cross-sectional study with a sample of 1500 students, representing the population of the state schools of Minas Gerais, involving the administration of a semi-structured questionnaire. The data were analyzed using simple frequency, mean, standard deviation, Fisher's exact test, the chi-square test and logistic regression (p < 0.05, CI 95%). The effective acceptance of the program was 28.8% and the effective adhesion to the program was 45.1%. Program acceptance was significantly higher among males and students who consumed less extra-institutional food. Acceptance and adhesion to the program was significantly higher among the older students and those who reported participating in activities related to nutritional education. In total, 73.5% of the students suggested improvements in school food. Many of the program's norms and guidelines are not being implemented. The acceptance of school food was negatively influenced by the consumption of extra-institutional foods and positively influenced by food and nutritional education activities.