http://www.bdtd.uerj.br/handle/1/3554 2026-03-14T17:16:03Z http://www.bdtd.uerj.br/handle/1/25474 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 2023-07-20T00:00:00Z http://www.bdtd.uerj.br/handle/1/25472 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 2025-12-01T00:00:00Z http://www.bdtd.uerj.br/handle/1/25456 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 2022-06-29T00:00:00Z http://www.bdtd.uerj.br/handle/1/25333 Título: Avaliação da resposta adipogênica à p-sinefrina em células 3T3-L1 Autor: Pereira, Mariana Maciel Primeiro orientador: Silva, Simone Vargas da Abstract: Obesity is a disease characterized by excessive body fat accumulation, the leading risk factor for developing associated comorbidities such as cardiovascular disease, type 2 diabetes mellitus, and certain types of cancer. Citrus aurantium L. has been used as an alternative to weight loss, with fewer adverse effects than most other pharmacological therapies. Commercially, C. aurantium is standardized in p- synephrine, its active ingredient with β3 adrenergic receptor agonist action, used to reduce adiposity and stimulate thermogenesis. In this study, we evaluated the adipogenic response of 3T3-L1 preadipocytes to isolated synephrine. The results show that p-synephrine did not affect cell viability and proliferation in any of the doses studied. After 96 hours of differentiation, p-synephrine (10 µM) inhibited the differentiation of 3T3-L1 preadipocytes and, after 48 hours, p-synephrine seems to inhibit the accumulation of triglycerides in these cells. We demonstrate that 3T3-L1 preadipocytes express the β3 adrenergic receptor (ADBR3), and the induction of differentiation did not alter the expression of this receptor in cells in all times analyzed. We evaluated the effect of p-synephrine on the protein expression of the two main browning markers (PGC-1α and UCP-1). Although p-synephrine does not alter the expression of PGC1-α, the presence of the differentiation medium was able to increase its protein expression. After 48 hours of incubation, p-synephrine induced an increase in the protein expression of UCP-1 in the absence of the differentiation medium. We also analyzed the gene expression of leptin, adiponectin, and TNF-α. P-synephrine seems to decrease leptin gene expression after 24 hours of differentiation while not altering adiponectin and TNF-α expression in any studied group and time. Until the moment, we concluded that p-synephrine acts by inhibiting the differentiation of 3T3-L1 preadipocytes. However, more research is needed to unravel the mechanisms involved in this event. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação 2021-11-16T00:00:00Z