Association of Fructo-oligosaccharides and Arginine Improves Severity of Mucositis and Modulate the Intestinal Microbiota.

Mucositis is defined as inflammatory and ulcerative lesions along of the gastrointestinal tract that leads to the imbalance of the intestinal microbiota. The use of compounds with action on the integrity of the intestinal epithelium and their microbiota may be a beneficial alternative for the prevention and/or treatment of mucositis. So, the aim of this study was to evaluate the effectiveness of the association of fructo-oligosaccharides (FOS) and arginine on intestinal damage in experimental mucositis. BALB/c mice were randomized into five groups: CTL (without mucositis + saline), MUC (mucositis + saline), MUC + FOS (mucositis + supplementation with FOS-1st until 10th day), MUC + ARG (mucositis + supplementation with arginine-1st until 10th day), and MUC + FOS + ARG (mucositis + supplementation with FOS and arginine-1st until 10th day). On the 7th day, mucositis was induced with an intraperitoneal injection of 300 mg/kg 5-fluorouracil (5-FU), and after 72 h, the animals were euthanized. The results showed that association of FOS and arginine reduced weight loss and oxidative stress (P < 0.05) and maintained intestinal permeability and histological score at physiological levels. The supplementation with FOS and arginine also increased the number of goblet cells, collagen area, and GPR41 and GPR43 gene expression (P < 0.05). Besides these, the association of FOS and arginine modulated intestinal microbiota, leading to an increase in the abundance of the genera Bacteroides, Anaerostipes, and Lactobacillus (P < 0.05) in relation to increased concentration of propionate and acetate. In conclusion, the present results show that the association of FOS and arginine could be important adjuvants in the prevention of intestinal mucositis probably due to modulated intestinal microbiota.

Lecithin-based nanocapsule loading sucupira (Pterodon emarginatus) oil effects in experimental mucositis.

Intestinal mucositis (IM) is a frequent adverse effect in anticancer therapy without standard treatment. The oil obtained from sucupira (Pterodon emarginatus) has anti-inflammatory properties, and the soybean lecithin reduces the intestinal toxicity of several xenobiotics. However, their water insolubility impairs the in vivo application. For this reason, we evaluated if the nanoencapsulation of sucupira oil (SO) in lecithin-based nanocapsules (SO-NC) could be a therapeutically effective system for the treatment of IM in murine cisplatin (CDDP)-induced intestinal mucositis model. SO was analyzed by LC-HRMS/MS and HPLC. SO-NC was prepared by nanoprecipitation and characterized using DLS, HPLC, and AFM. Mice body weight and food consumption were assessed daily during experimental mucositis induced by CDDP. The animals were euthanized, and intestinal permeability, inflammatory mediators, and intestinal histology were performed. SO-NC demonstrated adequate characteristics for oral administration as size under 300 nm, IP < 0.3, high EE, and spherical shape. In vitro cytotoxicity performed against RAW 264.7 cell lines resulted in cell viability above 80 % confirming the non-cytotoxic profile of SO (IC50 268 µg/mL) and SO-NC (IC50 118.5 µg/mL) up to 117.2 µg/mL. The untreated mice showed intestinal toxicity after i.p. of CDDP, principally weight loss, increased intestinal permeability, and MPO and TNF-α levels. Surprisingly, the administration of SO to CDDP-mucositis animals did not circumvent the CDDP effects and increased intestinal permeability. However, SO-NC proved efficient in mitigating the experimental intestinal mucositis by improving intestinal epithelium architecture, reducing intestinal permeability, and improving the MPO levels. In conclusion, SO-NC can positively impact intestinal mucositis by promoting mucosal recovery. This is a promising strategy for developing a new treatment for intestinal mucositis.

Baseline Pro-inflammatory Diet Is Inversely Associated with Change in Weight and Body Fat 6 Months Following-up to Bariatric Surgery.

OBJECTIVE: To evaluate whether the baseline Dietary Inflammatory Index (DII®) was associated with weight loss and body composition change after bariatric surgery. METHODOLOGY: This longitudinal study included 132 women with obesity (BMI ≥ 35 kg/m2, 43.0 ± 9.7 years), followed up for 6 months after bariatric surgery. The DII® was calculated from dietary data collected using 24-h dietary recall interviews. Anthropometric variables, socio demographic variables, health-related habits, history of disease, as well as gastrointestinal symptoms, both in the preoperative period (baseline) and 6 months after bariatric surgery were collected from the patients' medical records. RESULTS: Individuals with a more pro-inflammatory diet (DII > 0.35 median value) preoperatively experienced smaller weight loss (- 22.7% vs. - 25.3%, p = 0.02) and fat mass loss (- 31.9 vs. - 36.2%, p = 0.026), with no difference in lean mass (p = 0.14). In a linear regression model, the baseline DII score was negatively associated with percentage change in weight and fat mass and positively associated with weight and fat mass in the sixth month after surgery. In addition, a pro-inflammatory baseline DII score was correlated with a lower intake of fruit (r = - 0.26, p = 0.006), vegetables (r = - 0.47, p = 0.001), and legumes (r = - 0.21, p = 0.003) in the postoperative period. CONCLUSION: In this longitudinal study, a pro-inflammatory diet at baseline was associated with smaller reductions in weight and body fat and poorer dietary quality (reduced consumption of fruits, vegetables, and legumes) 6 months after bariatric surgery.

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

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 24h and 72h 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-κB. These changes persisted after 72h. While signs of intestinal toxicity were also observed 24h after administration of SpHL-CDDP, after 72h 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, 72h 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-κB. 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.

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.

Efeitos da ingestão de diferentes fontes lipídicas na mucosite em camundongos submetidos à quimioterapia com ARA-C / Effects of the intake of different lipid sources in mucositis in mice undergoing chemotherapy with ARA-C

Os lipídeos desempenham importante papel no metabolismo, na composição estrutural, transmissão de sinais celulares e na função imunológica do organismo. Os diferentes ácidos graxos que compõem os triacilgliceróis e fosfolípides vão ditar o tipo de resposta orgânica. Os agentes antineoplásicos são drogas amplamente utilizadas no tratamento de diversos tipos de câncer, tratamento este que, muitas vezes, resulta em efeitos colaterais responsáveis pela restrição da dose e sucesso da quimioterapia. Assim, dietas que previnam os efeitos deletérios da quimioterapia poderiam ser utilizadas como coadjuvantes no tratamento do câncer ou quimioterapia. Este trabalho teve por objetivo verificar a ação do consumo de diferentes fontes lipídicas à base de ácidos graxos ômega-3 (óleo de linhaça), triacilgliceróis de cadeia média (gordura de coco) e ácidos graxos trans (gordura vegetal hidrogenada) no trofismo intestinal de camundongos submetidos a tratamento com o quimioterápico (citarabina). Analisando o efeito da citarabina neste estudo, verificou-se que essa droga agrediu o organismo, causando perda de peso dos camundongos, diminuição da massa celular intestinal (sugerida pela redução no teor de DNA da mucosa intestinal) e relativo aumento da proteína na mucosa intestinal, principalmente nos animais alimentados com óleo de soja. As demais fontes lipídicas não alteraram os efeitos vistos pelo uso da citarabina. Os resultados sugerem, nas condições realizadas, não haver na utilização das fontes lipídicas citadas concomitantemente à aplicação da citarabina influência benéfica sobre e tratamento, sendo que a ingestão de óleo de soja pela sua riqueza em ácidos graxos ômega-6, poderia piorar o processo inflamatório decorrente da quimioterapia.

Lipids play an important role in metabolism, in the structural composition, in the transmission of cellular signals and in the body immune function. The different fatty acids that make up lhe triacylglycerols and phospholipids will dictate the type of organic response. The antineoplastic agents are widely used drugs in the treatment of various cancers, a treatment that often results in side effects responsible for restricting the rate and success of the chemotherapy. Thus, diets that prevent the deleterious effects of chemotherapy could be used as adjunct treatment of cancer or chemotherapy. This work was aimed at investigating the effects of the consumption of several lipid-based omega-3 (flaxseed oil), medium chain triglycerides (coconut) and Trans fatty acids (hydrogenated vegetable fat) in the intestinal tropism of mice treated with chemotherapy (cytarabine). Analyzing the effect of cytarabine in this study, it was found that this drug damaged the body, causing weight loss in mice, decreased intestinal cell mass (suggested by the reduction in the DNA content of the intestinal mucosa) and relative increase of protein in the intestinal mucosa mainly in animals fed with soybean oil. The other fat sources did not alter the effect seen by the use of cytarabine. The results suggest, in the existing conditions, that there is no beneficial influence on the treatment due to the use of the mentioned lipid sources concomitantly to the application on the cytarabine, and the intake of soybean oil, for its richness in Omega-6, could exacerbate the inflammatory process resulting from the chemotherapy.

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.

Omega-3 fatty acids reduce the development of preneoplasic lesions

Objective: The purpose of this study was to evaluate the anticancer potential of dietary omega-3 supplementation toreduce induced intestinal preneoplastic lesions in Wistar rats. Methods: A total of 58 11-week-old male Wistar rats (Rattus norvergicus, albinus variety, Rodentia) were distributed into two groups: a control group (n=25) and an omega-3-treated group (n=28). Aberrant crypt foci were induced by 1,2-dimethylhydrazine. Tissue incorporation of the supplemented omega-3 fatty acids was evaluated by determining the fatty acid profiles of intra-abdominal fat and the liver with gas chromatography.Results: The omega-3 group presented lower weight and lower food intake (p<0.05) than the control group. Thenumber of aberrant crypt foci decreased 55.34% in response to omega-3 supplementation. Foci with more than three crypts decreased 57.14% between weeks 13 and 28. There was no statistical difference for the docosahexaenoic acid content in the liver of the omega-3 group between week 6 and weeks 13 and 28. Conclusion: These results suggest that omega-3 may slow the progress of colorectal carcinogenesis.

Objetivo: O objetivo do estudo foi avaliar o potencial anticarcinogênico da suplementação com ômega-3 em reduzirlesões pré-neoplásicas induzidas em intestino de ratos Wistar. Métodos: Ratos Wistar machos, com 11 semanas de idade (Rattus norvergicus), foram subdivididos em dois grupos: grupo controle (n=25) e grupo ômega-3 (n=28). Os focus de criptas aberrantes foram induzidos pela 1,2 dimetilhidrazina. A incorporação dos ácidos graxos ômega-3 suplementados foi avaliada pela identificação do perfil de ácidos graxos da gordura intra-abdominal e do fígado por cromatografia gasosa. Resultados: O grupo ômega-3 apresentou menor consumo da dieta e menor ganho de peso (p<0,05) do que o grupo controle. O número de focus de criptas aberrantes foi reduzido em 55,34% como conseqüência da suplementação dietética com ômega-3. Os focus com três ou mais do que três criptas diminuíram 57,14% entre a 13ª a 28ª semanas. Não foi verificada diferença estatística para o conteúdo de ácido docosahexaenóico. Conclusão: O resultado sugere que o ômega-3 pode reduzir a evolução da carcinogênese colorretal.

Efeito da goma guar parcialmente hidrolisada no metabolismo de lipídeos e na aterogênese de camundongos / Effect of partially hydrolyzed guar gum on lipid metabolism and atherogenesis of mice

OBJETIVO: Observar os efeitos da goma guar parcialmente hidrolisada no metabolismo de colesterol e na formação de placa aterosclerótica em aorta de camundongos deficientes no receptor LDL, euglicêmicos ou com hiperglicemia induzida por estreptozotocina. MÉTODOS: Trinta e seis camundongos deficientes para o receptor de LDL foram divididos em quatro grupos de nove animais: grupos euglicêmicos, alimentados com dieta aterogênica padrão (controle euglicêmico) ou suplementada com 7,5 por cento de goma guar parcialmente hidrolisada (goma guar parcialmente hidrolisada euglicêmico) e grupos hiperglicêmicos alimentados com dieta aterogênica padrão (controle hiperglicêmico) ou suplementada com 7,5 por cento de goma guar parcialmente hidrolisada (goma guar parcialmente hidrolisada hiperglicêmico). Após quatro semanas de experimento foram medidos: ingestão alimentar, ganho de peso, glicemia, colesterol plasmático e hepático, assim como lesão aterosclerótica na aorta torácica e abdominal. RESULTADOS: Os resultados mostram que a suplementação de goma guar parcialmente hidrolisada levou ao aumento do colesterol hepático e plasmático em animais euglicêmicos, mas sem aumento na área de lesão aterosclerótica na aorta. Em animais hiperglicêmicos, a redução no colesterol plasmático não foi estatisticamente significante, mas no que se refere à lesão da aorta, observou-se redução significante. CONCLUSÃO: Os resultados sugerem que a goma guar parcialmente hidrolisada pode reduzir a aterosclerose associada ao Diabetes Mellitus tipo 1.

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 percent of partially hydrolyzed guar gum and streptozotocin-induced hyperglycemic groups also fed an atherogenic diet without or supplemented with 7.5 percent 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.