Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine.

Abstract Hypertriglyceridemia is associated with several metabolic diseases. The triglycerides (TG) disrupt the cholesterol reverse transport and contribute to increased levels of low-density lipoprotein (LDL). High-density lipoprotein (HDL) acts in cholesterol reverse transport as an anti-inflammatory and antioxidant. This study aims to investigate the role of hypertriglyceridemia in the functionality of HDL. Individuals were divided into 4 groups based on high or low HDL-c and triglycerides levels. Biochemical and anthropometric analysis were performed. This study demonstrated that triglycerides promote dysfunctions on HDL, increasing the cardiovascular risk. Blood pressure was higher in subjects with low HDL. Women presented higher levels of HDL-c and low percentage of fat mass. The highest levels of triglycerides were observed in older age. In addition, high levels of triglycerides were associated with higher total cholesterol and LDL-c levels, non-HDL-c, non-esterified fatty acids, and blood glucose, increasing in the ratio of non-HDL-c/HDL-c and ApoB/ApoA-I. The increase of triglycerides levels progressively impairs the antioxidant capacity of HDL, probably due to a higher occurrence of fatty acid peroxidation in individuals with hypertriglyceridemia. Patients with high HDL and low TG levels increased the Lag Time. Furthermore, a positive correlation was found between TG versus HDL particle size, variables that depend on age and anthropometric parameters.

ABSTRACT Diabetes mellitus (DM) is a disease associated with delayed wound healing of oral ulcers by increased expression of proinflammatory cytokines and cellular apoptosis. Objective to evaluate the influence of Tumor Necrosis Factor alpha (TNF-α) and apoptosis in rats with DM treated with chamomile extract or triamcinolone. Material and Methods Wistar male rats (210.0±4.2 g) were divided into five groups: negative control group (NCG) without diabetes; positive control group (PCG) with DM (alloxan, 45 mg/kg); and groups treated with chamomile extract (normoglycemic= NCG group and diabetic= DCG group) and with triamcinolone (TG). Traumatic ulcers were performed on all animals that received topical triamcinolone, chamomile extract or saline 12/12 hours for ten days. Results On days five and ten the animals were euthanized and the ulcers were analyzed by light microscopy, TUNEL assay, and immunohistochemically (TNF-α). The NCG (p=0.0062), PCG (p=0.0285), NCG (p=0.0041), and DCG (p<0.0001) groups were completely healed on the 10th day, however, there was no healing on the TG (p=0.5127) group. The TNF-α expression showed a significant reduction from the 5th to the 10th day in NCG (p=0.0266) and DCG (p=0.0062). In connective tissue, the TUNEL assay showed a significant reduction in the number of positive cells in NCG (p=0.0273) and CNG (p=0.0469) and in the epithelium only in CDG (p=0.0320). Conclusions Chamomile extract can optimize the healing of traumatic oral ulcers in diabetic rats through the reduction of apoptosis in the epithelium and TNF-α expression.

Onze derivados da ftalimida foram avaliados quanto a sua atividade antiproliferativa em células tumorais e normais e possíveis efeitos tóxicos. Avaliou-se a citotoxicidade contra tumores murinos (células de Sarcoma 180 e B-16/F-10) e células mononucleares do sangue perférico (CMSP) usando os ensaios de MTT e Alamar Blue. Em seguida, a investigação de citotoxicidade foi executada por citometria de fluxo e potencial antitumoral e toxicológico por meio de métodos in vivo. As moléculas 3b, 3c, 4 e 5 revelaram citotoxicidade in vitro contra Sarcoma 180, B-16/F-10 e PBMC. Uma vez que o composto 4 foi o derivado mais efetivo, ele foi escolhido para detalhar o mecanismo de ação após 24, 48 e 72h de exposição (22.5 e 45 µM). Células de Sarcoma 180 tratadas com o composto 4 mostraram desintegração de membrana, fragmentação de DNA e despolarização mitocondrial de maneira tempo e concentracão dependente. Os compostos 3c, 4 e 5 (50 mg/kg/dia) não inibiu o crescimento tumoral in vivo. Os animals tratados com o composto 4 exibiram aumento do total de leucócitos, linfócitos e no peso relativo do baço, diminuição de neutrófilos e hiperplasia da polpa branca esplênica. Os animais tratados apresentaram alterações histológicas reversíveis. A molécula 4 tem ação antiproliferativa in vitro provavelmente por ativação de apoptose, efeitos tóxicos reversíveis e exibiu propriedades imunoestimulantes que podem ser exploradas para atacar células neoplásicas.

Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells) and peripheral blood mononuclear cells (PBMC) using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM). Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day) did not inhibit in vivotumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells.

Objetivou-se com este trabalho avaliar a influência de diferentes dietas líquidas sobre os perfis dos metabólitos séricos relacionados ao status proteico e energético de bezerros até 60 dias de idade. Foram utilizados 24 bezerros mestiços, distribuídos em delineamento inteiramente casualizado com quatro tratamentos e seis repetições: leite integral (controle); 50% leite integral + 50% de soro de queijo in natura; 50% leite integral + 50% de soro de queijo in natura + um ovo integral in natura; 50% leite integral + 50% de soro de queijo in natura + um ovo integral in natura + biotina. A adaptação dos animais às dietas compreendeu os dez dias que antecederam o início da pesquisa. Os animais tiveram à disposição concentrado farelado, feno de capim Tifton-85 (Cynodon sp.) e água ad libitum. Semanalmente, foram coletadas amostras de sangue por punção da veia jugular externa, no período da manhã, antes do fornecimento da dieta líquida e duas horas após a ingestão desta. As concentrações médias de glicose, ureia, creatinina, proteínas séricas totais e albumina mostraram-se dentro dos limites normais para bezerros e, apenas os valores de ureia diferiram estatisticamente entre os tratamentos, sem prejudicar, porém, o desempenho normal dos animais. Assim, pôde-se utilizar o soro em substituição ao leite integral, na proporção de 50%, sem adição de ovo ou biotina, uma vez que os mesmos também não acarretaram alterações nas concentrações séricas dos metabólitos estudados.

This study was conducted to evaluate the influence of the liquid diet on the blood metabolites profile related to the protein and energy status of calves receiving different liquid diets. Twenty-four calves of Holstein x Gir breed were distributed in a completely randomized design with four treatments and six replications: Whole milk (Control); 50% whole milk + 50% of whey of cheese in natura; 50% whole milk + 50% of cheese whey in natura + one egg in natura; 50% whole milk + 50% of cheese whey in natura + one egg in natura + of biotin. The adaptation of the animals to the experimental diets occurred ten days before the beginning of the treatments. The animals received concentrate, Tifton-85 (Cynodon sp.) hay and water ad libitum from the birth to wean. Samples of blood were weekly collected in the morning, before the supply of the liquid diet and two hours after the ingestion. The concentrations of glucose, urea, creatinin, total proteins and albumin found in the serum of the calves, between liquid diets tested, were within normal limits when compared to reference levels in the literature. Only the values of urea differ significantly between treatments, but without harming the performance of the animals, soon it can be used the cheese whey in substitution to the whole milk, in the proportion of 50%, without egg or biotin addition, for a redution on the production cost.