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Efeito da exposição combinada de cafeína e etanol durante o desenvolvimento no comportamento de camundongos adultos no teste da grade elevada

2026-03-13T16:43:02Z

Título: Efeito da exposição combinada de cafeína e etanol durante o desenvolvimento no comportamento de camundongos adultos no teste da grade elevada Autor: Cruz, Vinicius Maia da Primeiro orientador: Filgueiras, Cláudio Carneiro Abstract: The consumption of alcoholic beverages during pregnancy is responsible for a series of neurobehavioral disorders such as motor and cognitive deficits. However, the mechanisms involved in the manifestation of these disorders poorly understood. Some studies suggest that caffeine consumption may interfere with the teratogenicity of ethanol. In this work, we aimed to evaluate in adult mice whether exposure to ethanol and/or caffeine during development altered motor coordination as well as the functional recovery after sensory deprivation resulting from the removal of vibrissae in the elevated grid test. Swiss mice were exposed from the first gestational day to the 21st postnatal day (PN21) to caffeine solution of 0.3 g/L (CAF group) or drank only filtered tap water (H2O group). Every other day, from PN2 to PN8, animals in each litter were intraperitoneally injected with 5 g/kg of ethanol (ETOH group) or equivalent volume of saline solution (SAL group). From PN75, the animals were submitted to the elevated grid test (4 experimental sessions; session duration: 1 minute; interval between sessions: 72h). From the 2nd to the 4th session, the animals had the mystacial vibrissae shaved 24h before each session. In each session, the number of correct steps (CS) and errors (E) and the error percentage 100xE/(CS+E)) committed by each forepaw while the animal moved along the grid were recorded. In the first session, the group of animals exposed to caffeine (CAF+SAL and CAF+ETOH) presented a higher % of error than H2O+SAL group. Although the % error in the group exposed to ethanol (ETOH+H2O) was higher than those presented by SAL+H2O group, this difference was close to statistical significance. In the second session, removal of vibrissae promoted a significant increase in the % of errors in all groups, that did not change along subsequent sessions. Our data suggest that exposure to caffeine during development impairs motor coordination, even after a long period without contact with the substance. The impairments in motor coordination caused by early exposure to ethanol were less evident than those caused by caffeine. Furthermore, we did not observe any interaction (synergism or attenuation) between caffeine and ethanol on behavior. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação

Efeito da suplementação com ômega-3 durante a gestação de fêmeas obesas: modulação da glicemia fetal e prevenção de alterações cardíacas associadas à programação cardiometabólica

2026-03-13T16:40:50Z

Título: Efeito da suplementação com ômega-3 durante a gestação de fêmeas obesas: modulação da glicemia fetal e prevenção de alterações cardíacas associadas à programação cardiometabólica Autor: Reis, Milena Avelar Primeiro orientador: Marques, Erika Afonso Costa Cortez Abstract: Maternal obesity impairs offspring cardiac development, leading to adverse extracellular matrix remodeling and delayed cardiomyocyte differentiation and maturation, which may be related to the advent of cardiovascular diseases later in life. Evidence suggests that maternal omega-3 supplementation during pregnancy has anti-inflammatory properties and potential beneficial effects on fetal development. Thus, this study aimed to evaluate the effect of omega-3 supplementation on fetal cardiometabolic alterations in the offspring of obese female Swiss mice. First, mothers were metabolically programmed by overfeeding during lactation, using the experimental model of litter size reduction. After birth, litters were adjusted to nine pups and allocated into the following groups: Maternal Overfed Group (GHM), with reduction to three females on the 3rd day of life, and Maternal Control Group (GCM), maintained with nine pups until the end of lactation. At the end of the lactation period, both groups received water and standard commercial chow ad libitum. When females from both groups reached 75 days, they were subdivided into four groups (n=6 each): GCM-ω3 and GHM-ω3 (supplemented with omega-3) and GCM-Ag and GHM-Ag (which received only water). After 15 days of initiation of the supplementation, females were mated with healthy males and supplemented until the 18th day of gestation, when they were euthanized and their fetuses analyzed. Before supplementation, females from the GHM group exhibited hyperphagia, increased body mass, adiposity, hyperglycemia, and glucose intolerance compared to GCM. Omega-3 supplementation prevented hyperphagia, excessive weight gain, and improved glucose tolerance in GHM-ω3 group compared to GHM-Ag. In GHM-Ag fetuses, hyperglycemia, increased cardiac levels of TNF-α and collagen deposition in the cardiac extracellular matrix were observed. These effects were prevented by maternal omega-3 supplementation in GHM-ω3 fetuses similar to those observed in control groups. Therefore, these findings indicate that maternal omega-3 supplementation may represent a promising nutritional strategy to reduce the impacts of gestational obesity on the offspring’s cardiometabolic programming. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação

Avaliação toxicogenética in vitro e in silico de três suplementos alimentares pré-treino

2026-03-11T17:57:58Z

Título: Avaliação toxicogenética in vitro e in silico de três suplementos alimentares pré-treino Autor: Dantas, Eduardo Kennedy Carrão Primeiro orientador: Felzenszwalb, Israel Abstract: In recent decades, the number of practitioners of physical activity has increased and, with it, the number of people who consume dietary supplements. However, some categories of food supplements, such as pre-workout, have gaps in the literature regarding safety in their use. There have already been studies that pointed to an association between the use of these supplements with liver disorders, for example, but they were unable to establish a causal relationship. Therefore, this work aims to investigate three food supplements: one investigated in article 1, and the other two analyzed in article 2, using in vitro approaches, at concentrations of 50, 5, 0.5, 0.05 and 0.005mg/mL, to evaluate the mutagenic potential, through the Salmonella/microsome assay, genotoxic, through the Micronucleus test, hepatocytotoxic through the WST-1, LDH, alkaline phosphatase and detection of glutathione activity (article 1), and in silico prediction for the pharmacokinetics and toxicity of the isolated compounds most present in In article 1, the supplement was able to induce mutagenicity in the TA98 strain at the highest concentration, in the presence of exogenous S9 mix metabolism 4%. In addition, it caused a genotoxic effect, leading to the generation of micronuclei, nucleoplasmic bridges and nuclear buds, and delay in the cell cycle, and a cytotoxic effect, decreasing the cell viability of HepG2 and F C 3H cells, in a dose- and time-dependent manner. dependent. In article 2, both supplements induced a mutagenic response in the five selected strains (TA97, TA98, TA100, TA102 and TA104), most of which were induced in the presence of metabolic activation. In addition, they showed genotoxic and cytotoxic effects on HepG2 and F C3H cells, similar to those seen in article 1. Furthermore, in this article, the glutathione activity assay revealed a decrease in glutathione levels, representing a deficiency in an important molecule for the balance of the redox state of cells. The results show the importance of metabolizing these supplements for them to exert their cytotoxic role. Plant extracts and central nervous system stimulants, present in the analyzed products, appear as possible candidates for the observed effects. The in silico results showed that few isolated compounds can cause toxic effects to the organism and interact with metabolizing enzymes as observed in the study. More studies should be carried out to elucidate the molecular mechanisms of toxicity of these supplements and the role of each substance present in the supplement in this context. Thus, this work appears as one more piece to be included in the body of evidence about these products and to emphasize the importance of their toxicological surveillance. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação

Integração tireoide, inflamação e sarcopenia na Doença Renal Crônica

2026-03-09T19:11:21Z

Título: Integração tireoide, inflamação e sarcopenia na Doença Renal Crônica Autor: Reis, Karina Schiavoni Scandelai Cardoso Primeiro orientador: Tavares, Ana Beatriz Winter Abstract: Thyroid dysfunction is common in chronic kidney disease (CKD) and tends to worsen with declining glomerular filtration rate (GFR), being modulated by factors such as proteinuria, malnutrition, and inflammation. In patients undergoing hemodialysis (HD), these disturbances amplify alterations in the thyroid–nutrition–muscle axis, which are associated with increased cardiovascular risk and mortality, despite the limited integrated evidence available addressing these mechanisms in this population. In this cross-sectional study, we investigated the association between thyroid function and CKD progression across different stages, analyzing its relationship with proteinuria and GFR in stages 3 and 4, as well as its interrelationships with nutritional status, inflammation, and sarcopenia in HD patients, in addition to developing a predictive model for identifying the risk of sarcopenia. The first article assessed the correlation between thyroid function and proteinuria in CKD stages 3 and 4. A total of 150 patients were included, 64 (42.6%) in stage 3 and 86 (59.3%) in stage 4, with a median age of 68 years (IQR 61–76). Median thyroid stimulating hormone (TSH), free T4 (FT4), and urinary protein-creatinine ratio (PCR) were 2.9 IU/mL (IQR 1.89–4.04), 1.26 ng/dL (IQR 1.10–1.41), and 315.5 mg/g (IQR 108.3–830), respectively. Proteinuria was detected in 91 patients (60.6%). There was a positive correlation between PCR and TSH (r = 0.23; p = 0.003) and a negative correlation between PCR and FT4 (r = –0.17; p = 0.03), suggesting that urinary protein loss may affect thyroid hormone metabolism. However, no significant differences in thyroid function were found between stages 3 and 4. The second article investigated the relationship among thyroid function, nutritional status, sarcopenia, and inflammation in 101 HD patients and 33 controls. The median age was higher in HD patients compared to controls (58 vs. 48 years, respectively). Thyroid autoimmunity was less prevalent in HD (6.9%) than in controls (18.1%). Compared with controls, HD patients exhibited higher TSH, C-reactive protein, interleukin-6, tumor necrosis factor α, and leptin levels, and lower FT3, FT4, albumin, and Geriatric Nutritional Risk Index (GNRI) values (p < 0.05), with no difference in BMI. Handgrip strength, skeletal muscle mass, and skeletal muscle mass index were significantly lower in HD patients. Sarcopenia was more frequent in HD patients (48.5% probable; 26.7% confirmed) than in controls (18.1% and 6%). Within the HD group, sarcopenic individuals showed significantly lower FT3 levels. A penalized regression model (Elastic Net) identified four independent predictors of sarcopenia: FT3, TSH, GNRI and dialysis status. Each 1 mIU/L increase in TSH raised the probability of sarcopenia by 6.6% (OR ≈ 1.07), while each 1 pg/mL increase in FT3 reduced the risk by 18% (OR ≈ 0.82). GNRI had a modest protective effect, and HD status increased the odds by 47% (OR ≈ 1.47). In summary, HD patients exhibit thyroid dysfunction, heightened inflammation, and poor nutritional status conditions closely associated with sarcopenia. FT3, TSH, GNRI and being on HD emerge as integrated risk markers for sarcopenia, underscoring the need for a multidimensional clinical approach targeting the thyroid–nutrition–muscle axis. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese