Jacqueline Isaura Alvarez Leite

The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation

BackgroundThis study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines.MethodsMice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 \ groups (control, colitis, HFD and colitis + HFD).ResultsObesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group.ConclusionOur results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream.

Effect of maternal diet rich in omega-6 and omega-9 fatty acids on the liver of LDL receptor-deficient mouse offspring.

BACKGROUND Omega-6 fatty acids are important to fetal development. However, during gestation/lactation, these fatty acids may contribute toward the development of fat tissue. Omega-9 fatty acids are associated with a reduction in serum lipids and protection from liver disease. OBJECTIVES The present study investigated the effect of the maternal intake of omega-6 and omega-9 in hypercholesterolemic mothers on the liver of the offspring. METHODS LDL receptor-deficient mice were fed a diet rich in either omega-6 (E6D) or omega-9 (E9D) for 45 days prior to mating and until the birth of the offspring, evaluating the effect on the offspring liver in comparison to a standard diet (STD). RESULTS Mothers fed with the E6D experienced an increase in total cholesterol (TC) and the offspring exhibited an increase in TC, hepatic triglycerides (TG), and CC-chemokine ligand (CCL)2/monocyte chemoattractant protein (MCP)-1 as well as a reduction in HDL. Histological analysis on this group revealed steatosis, leukocyte infiltrate, and increased CCL2/MCP-1 expression. The ultrastructural analysis revealed hepatocytes with lipid droplets and myofibroblasts. The offspring of mothers fed the standard diet exhibited low serum TC, but microvesicular steatosis was observed. The offspring of mothers fed the E9D exhibited lower serum and hepatic TG as well as higher LDL in comparison to the other diets. The histological analyses revealed lower steatosis and leukocyte infiltrate. CONCLUSIONS The findings suggest that hypercholesterolemic mothers with a diet rich in omega-6 fatty acids predispose their offspring to steatohepatitis, whereas a diet rich in omega-9 has a protective effect.

Impact of Nutrients and Food Components on Dyslipidemias: What Is the Evidence?

Dyslipidemias have been shown to bear a close association with an increased risk of cardiovascular diseases, atherosclerosis in particular. As efforts are being made to find alternative therapies and ways to prevent disease, there is a corresponding rise in public interest in food and/or active food components that contribute to an improved lipid profile and, thus, to better health. Besides supplying the basic nutrients necessary for well-being, some foods add further physiologic benefits. In fact, specific foods and bioactive components could be beneficial in controlling dyslipidemias. From a review of the literature on foods and bioactive compounds, their recommended quantities, and expected effects, we found that the following nutrients and food components could positively impact the lipid profile: monounsaturated and polyunsaturated fatty acids, soluble fiber, vegetable proteins, phytosterols, and polyphenols. Therefore, incorporating these components into the regular diets of individuals is justified, because they contribute additional positive effects. This suggests that they also be recommended in clinical practice.

White tea (Camellia sinensis) extract reduces oxidative stress and triacylglycerols in obese mice

White tea is an unfermented tea made from young shoots of Camellia sinensis protected from sunlight to avoid polyphenol degradation. Although its levels of catechins are higher than those of green tea (derived from the same plant), there are no studies addressing the relationship between this tea and obesity associated with oxidative stress.The objective of this study was to evaluate the effect of white tea on obesity and its complications using a diet induced obesity model. Forty male C57BL/6 mice were fed a high-fat diet to induce obesity (Obese group) or the same diet supplemented with 0.5% white tea extract (Obese + WTE) for 8 weeks. Adipose tissue, serum lipid profile, and oxidative stress were studied. White tea supplementation was not able to reduce food intake, body weight, or visceral adiposity. Similarly, there were no changes in cholesterol rich lipoprotein profile between the groups. A reduction in blood triacylglycerols associated with increased cecal lipids was observed in the group fed the diet supplemented with white tea. White tea supplementation also reduced oxidative stress in liver and adipose tissue. In conclusion, white tea extract supplementation (0.5%) does not influence body weight or adiposity in obese mice. Its benefits are restricted to the reduction in oxidative stress associated with obesity and improvement of hypertriacylglycerolemia.

Omega-3 fatty acids reduce the development of preneoplasic lesions

OBJETIVO: O objetivo do estudo foi avaliar o potencial anticarcinogenico da suplementacao com omega-3 em reduzir lesoes pre-neoplasicas induzidas em intestino de ratos Wistar. METODOS: Ratos Wistar machos, com 11 semanas de idade (Rattus norvergicus), foram subdivididos em dois grupos: grupo controle (n=25) e grupo omega-3 (n=28). Os focus de criptas aberrantes foram induzidos pela 1,2 dimetilhidrazina. A incorporacao dos acidos graxos omega-3 suplementados foi avaliada pela identificacao do perfil de acidos graxos da gordura intra-abdominal e do figado por cromatografia gasosa. RESULTADOS: O grupo omega-3 apresentou menor consumo da dieta e menor ganho de peso (p<0,05) do que o grupo controle. O numero de focus de criptas aberrantes foi reduzido em 55,34% como consequencia da suplementacao dietetica com omega-3. Os focus com tres ou mais do que tres criptas diminuiram 57,14% entre a 13a a 28a semanas. Nao foi verificada diferenca estatistica para o conteudo de acido docosahexaenoico. CONCLUSAO: O resultado sugere que o omega-3 pode reduzir a evolucao da carcinogenese colorretal.

Intestinal toxicity evaluation of long-circulating and pH-sensitive liposomes loaded with cisplatin

Abstract Cisplatin (CDDP) is a chemotherapeutic agent widely used in several anticancer protocols for instance head and neck, testicle, ovarian, lung and peritoneal carcinomatosis. According to the literature, the use of CDDP is associated with several side effects; among them, we highlighted the mucositis. CDDP, when administered by IP, promoted significant intestinal epithelium alterations in an experimental model. Our research group has proposed that the incorporation of CDDP into long‐circulating and pH‐sensitive liposomes (SpHL‐CDDP) could help to overcome some side effects induced by this drug. Thus, we evaluated signs of intestinal toxicity 24 h and 72 h after the administration of a single i.p dose of free CDDP or SpHL‐CDDP to healthy Swiss mice. Twenty‐four hours after administration of free CDDP, the mice showed signs of intestinal toxicity, principally weight loss, increased intestinal permeability associated with a decrease in expression of tight junctions, and histological damage with the presence of inflammatory infiltrates and activation of ERK1/2 and NF‐&kgr;B. These changes persisted after 72 h. While signs of intestinal toxicity were also observed 24 h after administration of SpHL‐CDDP, after 72 h body weight and intestinal permeability of mice in this group were similar to those of mice in the control group. In comparison with the free CDDP treatment group, 72 h after treatment mice in the SpHL‐CDDP group showed better histological parameters, lower levels of inflammatory infiltrate with increased IL‐10 and IgA levels, and less activation of caspase‐3, ERK1/2 and NF‐&kgr;B. These differences could account for the recovery of the intestinal epithelium observed in mice treated with SpHL‐CDDP but not in mice treated with free CDDP. In conclusion, here we show that encapsulation of CDDP in SpHL lessens intestinal damage and that, as such, SpHL‐CDDP is a promising candidate for clinical use. Graphical abstract Figure. No Caption available.

Leishmania major Self-Limited Infection Increases Blood Cholesterol and Promotes Atherosclerosis Development

Leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a Th1 proinflammatory response. Atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. In this study, we evaluated the influence of L. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein E-deficient (apoE KO) mice. After 6 weeks of infection, apoE KO mice exhibited reduced footpad swelling and parasitemia similar to C57BL/6 controls, confirming that both strains are resistant to infection with L. major. L. major-infected mice had increased plasma cholesterol levels and reduced triacylglycerols. With regard to atherosclerosis, noninfected mice developed only fatty streak lesions, while the infected mice presented with advanced lesions containing a necrotic core and an abundant inflammatory infiltrate. CD36 expression was increased in the aortic valve of the infected mice, indicating increased macrophage activation. In conclusion, L. major infection, although localized and self-limited in resistant apoE KO mice, has a detrimental effect on the blood lipid profile, increases the inflammatory cell migration to atherosclerotic lesions, and promotes atherogenesis. These effects are consequences of the stimulation of the immune system by L. major, which promotes the inflammatory components of atherosclerosis, which are primarily the parasite-activated macrophages.

Conjugated linoleic acid prevents damage caused by intestinal mucositis induced by 5-fluorouracil in an experimental model

BACKGROUND Studies have showed the protective effects of conjugated linoleic acid (CLA) on intestinal epithelium, modulating host immune and inflammatory responses on intestinal diseases. OBJECTIVE To evaluate the preventive effects of CLA on the intestinal mucositis induced by 5-FU in a murine model. METHODS Sixty-four BALB/c mice were randomly divided into four groups: Control (CTL), fed a standard chow diet; CLAs, fed a diet supplemented with CLA; Mucositis (5-FU), fed a standard chow diet and underwent mucositis induction and CLAs 5-FU, fed a diet supplemented with CLA and underwent mucositis induction. Mucositis was induced by intraperitoneal injection of 300 mg/kg 5-FU. After 72 h, the animals were euthanized and intestinal permeability, bacterial translocation, inflammatory mediators, and intestinal histology were evaluated. RESULTS Mice in the CLAs 5-FU group showed reduced weight loss compared to those in the 5-FU group (p < 0.005). Furthermore, the results also showed that the treatment with CLA reduced intestinal permeability, bacterial translocation, and biomarkers of inflammatory response besides minor damage to ZO-1 and occludin with maintenance of the integrity of the intestinal epithelium and a favorable balance between the inflammatory and regulatory cytokines. CONCLUSION This study suggests that CLA reduced the adverse effects from 5-FU administration on the intestinal mucosa.

Efeito da goma guar parcialmente hidrolisada no metabolismo de lipídeos e na aterogênese de camundongos

OBJECTIVE: The objective of this study was to observe the effects of partially hydrolyzed guar gum on cholesterol metabolism and atherosclerosis in the aorta of euglycemic and streptozotocin-induced hyperglycemic LDL receptor deficient mice. METHODS: Thirty six LDL receptor deficient mice were divided into 4 groups of 9 animals: euglycemic groups fed on hypercholesterolemic diet without or supplemented with 7.5% of partially hydrolyzed guar gum and streptozotocin-induced hyperglycemic groups also fed an atherogenic diet without or supplemented with 7.5% of partially hydrolyzed guar gum. After 4 weeks of experiment, food intake, body weight, glycemia, blood and liver cholesterol and atherosclerotic lesion in the aorta were determined. RESULTS: The results showed that partially hydrolyzed guar gum induced an increase in blood and liver cholesterol in euglycemic mice when compared with euglycemic control groups at the end of the experiment. On the other hand, although not affecting plasma cholesterol, hyperglycemic mice supplemented with partially hydrolyzed guar gum had the lesion area in the aorta significantly reduced. In hyperglycemic animals, plasma cholesterol did not decrease significantly but the lesion area in the aorta did. CONCLUSION: The present study suggests that partially hydrolyzed guar gum can reduce the development of atherosclerosis associated with type 1 diabetes mellitus.