Gluten worsens non-alcoholic fatty liver disease by affecting lipogenesis and fatty acid oxidation in diet-induced obese apolipoprotein E-deficient mice.

Obesity is closely associated with non-alcoholic fatty liver disease (NAFLD), characterized by hepatic fat accumulation and hepatocyte injury. Preclinical studies have shown exacerbated weight gain associated with an obesogenic gluten-containing diet. However, whether gluten affects obesity-induced hepatic lipid accumulation still remains unclear. We hypothesized that gluten intake could affect fatty liver development in high-fat diet (HFD)-induced obese mice. Thus, we aimed to investigate the impact of gluten intake on NAFLD in HFD-induced obese mice. Male apolipoprotein E-deficient (Apoe-/-) mice were fed with a HFD containing (GD) or not (GFD) vital wheat gluten (4.5%) for 10 weeks. Blood and liver were collected for further analysis. We found that gluten exacerbated weight gain, hepatic fat deposition, and hyperglycemia without affecting the serum lipid profile. Livers of the GD group showed a larger area of fibrosis, associated with the expression of collagen and MMP9, and higher expression of apoptosis-related factors, p53, p21, and caspase-3. The expression of lipogenic factors, such as PPARγ and Acc1, was more elevated and factors related to beta-oxidation, such as PPARα and Cpt1, were lower in the GD group compared to the GFD. Further, gluten intake induced a more significant expression of Cd36, suggesting higher uptake of free fatty acids. Finally, we found lower protein expression of PGC1α followed by lower activation of AMPK. Our data show that gluten-containing high-fat diet exacerbated NAFLD by affecting lipogenesis and fatty acid oxidation in obese Apoe-/- mice through a mechanism involving lower activation of AMPK.

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.

Oral supplementation with capsaicin reduces oxidative stress and IL-33 on a food allergy murine model.

BACKGROUND: Food allergy is an abnormal immune response to antigens introduced into the body through food. Its prevalence has increased in developed and developing countries. Natural products are traditionally used to alleviate and treat diseases, and diet can play a role in both the prevention and management of food allergy. The effects of capsaicin as an anti-oxidant, anticarcinogenic, and anti-inflammatory in the energy expenditure and suppression of fat accumulation have been demonstrated. This study evaluated the effect of oral supplementation with capsaicin on a food allergy model. METHODS: OVA-sensitized mice received ovalbumin solution, and they were fed with chow supplemented with capsaicin for 7 days. The control group received AIN-93 chow with no supplementation. IgE anti-ova, inflammatory infiltration, oxidative stress and metabolic analysis were performed. RESULTS: The results showed that capsaicin supplementation is not able to reduce characteristic signs of food allergy, such as production of IgE and weight loss. However, macrophages infiltration and IL-33 in proximal jejunum was reduced in OVA capsaicin group. In addition, hepatic triglycerides and intestinal hydroperoxides were reduced in both capsaicin groups. CONCLUSION: Oral supplementation with capsaicin attenuated important factors associated to food allergy such as inflammation and oxidative stress, suggesting better prognosis and evolution of the disease.

Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells.

Butyrate is a 4-carbon fatty acid that has antiinflammatory and antioxidative properties. It has been demonstrated that butyrate is able to reduce atherosclerotic development in animal models by reducing inflammatory factors. However, the contribution of its antioxidative effects of butyrate on atherogenesis has not yet been studied. We investigated the influence of butyrate on oxidative status, reactive oxygen species (ROS) release and oxidative enzymes (NADPH oxidase and iNOS) in atherosclerotic lesions of ApoE(-/-) mice and in oxLDL-stimulated peritoneal macrophages and endothelial cells (EA.hy926). The lesion area in aorta was reduced while in the aortic valve, although lesion area was unaltered, superoxide production and protein nitrosylation were reduced in butyrate-supplemented mice. Peritoneal macrophages from the butyrate group presented a lower free radical release after zymosan stimulus. When endothelial cells were pretreated with butyrate before oxLDL stimulus, the CCL-2 and superoxide ion productions and NADPH oxidase subunit p22phox were reduced. In macrophage cultures, in addition to a reduction in ROS release, nitric oxide and iNOS expression were down-regulated. The data suggest that one mechanism related to the effect of butyrate on atherosclerotic development is the reduction of oxidative stress in the lesion site. The reduction of oxidative stress related to NADPH oxidase and iNOS expression levels associated to butyrate supplementation attenuates endothelium dysfunction and macrophage migration and activation in the lesion site.

Papel da capsaicina de uso tópico em modelo murino de alergia alimentar / Topical use of capsaicin in murine model of food allergy

A alergia alimentar é uma reação de hipersensibilidade imediata mediada por lgE que ocorre com a ingestão de alimentos alergênicos após sensibilização prévia. t: considerada um importante problema de saúde pública mundial, afetando cerca de 7% de crianças e 2% de adultos, com crescente prevalência em países desenvolvidos e em desenvolvimento. Hipoteticamente, agentes anti-inflamatórios poderiam contribuir para o controle de algumas manifestações da alergia. Um candidato a tal efeito e a capsaicina (8-metil-N-6-vanilil-nonenamida), principal componente picante da pimenta, que possui ação analgésica e anti-inflamatória quando aplicada topicamente. Este estudo avaliou o efeito do uso t6pico de capsaicina nas manifestações da alergia alimentar. Para tanto, camundongos BALB/c foram sensibilizados com ovalbumina (OVA) com posterior desafio oral com solução de clara de ovo a 20%. A partir do desafio oral até a eutanásia, animais do grupo capsaicina (ALE-CAP) foram tratados com creme capsaicina a 0,075%, enquanto que animais alérgicos (ALE) foram tratados apenas com o creme base. Os resultados mostram o aumento da concentração sérica de lgE e lgG1 anti-OVA em ambos os grupos, como esperado pelo protocolo de sensibilização. Porém, em relação ao grupo alérgico(ALE), animais do grupo ALE CAP apresentaram um perfil mais favorável, como visto pela maior ingestão do alérgeno, menor perda de peso, redução da infiltração de eosinófilos e neutrófilos (avaliados indiretamente pela atividade de enzimas EPO eMPO, respectivamente) e menor produção de muco pelas células caliciformes. Os resultados sugerem que o tratamento t6pico com capsaicina leva a uma melhora de algumas das manifestações mais importantes da alergia como a inflamação intestinal e a perda de peso. Esse fato pode estar relacionado a inibição do canal TRPV1, atuando indiretamente em vias de sinalização de células TC04•, mast6citos e basófilos, aumentando o limiar de ativação de tais células e, assim...

Food allergy is an immediate hypersensitivity reaction mediated by lgE whichoccurs with the ingestion of allergenic foods after previous sensitization. It is considered a major problem of public health worldwide, affecting about 7% of childrenand 2% of adults, with increasing prevalence in developed and developing countries. Hypothetically, anti-inflammatory agents could contribute to the control some allergy symptoms. A candidate for this purpose is the capsaicin (8-methyl-N-vanillyl-6-nonenamide), the main pungent component of red pepper, having analgesic and anti- inflammatory actions when applied topically. This study evaluated the effect of topical treatment of capsaicin in some food allergy maniestations. For this purpose BALB/c mice were sensitized with ovalbumin (OVA) with subsequent oral challenge with 20% egg yolk solution. From the oral challenge to euthanasia, animals of capsaicin group(CAP) were topically treated with a capsaicin cream (0.075% in cream base) while the allergic group (ALE) were treated with the cream base (without capsaicin). The results showed that there was an increase in serum lgE and anti-OVA lgG1 in both groups, as expected with this from sensitization protocol. However, compared to allergic group(ALE), animals from CAP group presented a more favorable profile, as suggested by the higher intake of allergen, reduced weight loss, reduced eosinophil and neutrophilinfiltrations (assessed indirectly by the activity of the enzymes EPO and MPO, respectively) and lower production of mucus by goblet cells. The results suggest that topical treatment with capsaicin leads to an improvement of some of the most important manifestations allergy such as intestinal inflammation and weight loss. These effects may be related to inhibition of TRPV1 channel, acting indirectly on CD4+ T cell, mastcells and basophils signaling, increasing their activation thre shold and thus decreasing the inflammatory process...