ovalbumin and Endotoxemia

The consumption of Westernized diets leads to hyperphagia and obesity, as well as intestinal alterations. In the present study, we evaluated the effect of the administration of a grape seed proanthocyanidin extract (GSPE) at different time points on the modulation of intestinal barrier function (intestinal permeability and metabolic endotoxemia), in rats with high-fat/high-carbohydrate diet-induced obesity. Animals were fed a cafeteria diet (CAF) supplemented with a preventive (PRE-CAF) or simultaneously intermittent (SIT-CAF) GSPE treatment (500 mg/kg bw). Changes in the plasma levels of an orally administered marker of intestinal permeability (ovalbumin, OVA), lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) were analyzed after animals were fed the obesogenic diet for 8, 12 and 17 weeks. In addition, ex vivo variations in transepithelial electrical resistance (TEER), the expression of tight junction (TJ) genes and the activity of myeloperoxidase (MPO) in the small and large intestines were monitored at the end of the experiment. The CAF diet increased OVA, LPS, MPO and TNF-α levels, accompanied by decreased TEER values in the small and large intestines. Interestingly, both GSPE treatments prevented these detrimental effects of the CAF diet, being the SIT-CAF group the most effective after 17 weeks of diet intervention. For the first time, this study provides evidence of the ameliorative effect of a proanthocyanidin extract, administered before or together with an obesogenic diet, on barrier dysfunction, as measured by intestinal permeability and metabolic endotoxemia.

Topics: Administration, Oral; Animals; Diet, High-Fat; Dietary Supplements; Endotoxemia; Female; Gene Expression Regulation; Grape Seed Extract; Intestinal Mucosa; Intestines; Lipopolysaccharides; Obesity; Ovalbumin; Permeability; Proanthocyanidins; Rats, Wistar; Tight Junction Proteins; Tumor Necrosis Factor-alpha

The presence of the complement-derived anaphylatoxin peptides, C3a and C5a, in the lung can induce respiratory distress characterized by contraction of the smooth muscle walls in bronchioles and pulmonary arteries and aggregation of platelets and leukocytes in pulmonary vessels. C3a and C5a mediate these effects by binding to their specific receptors, C3aR and C5aR, respectively. The cells that express these receptors in the lung have not been thoroughly investigated, nor has their expression been examined during inflammation. Accordingly, C3aR and C5aR expression in normal human and murine lung was determined in this study by immunohistochemistry and in situ hybridization. In addition, the expression of these receptors was delineated in mice subjected to LPS- and OVA-induced models of inflammation. Under noninflamed conditions, C3aR and C5aR protein and mRNA were expressed by bronchial epithelial and smooth muscle cells of both human and mouse lung. C3aR expression increased significantly on both bronchial epithelial and smooth muscle cells in mice treated with LPS; however, in the OVA-challenged animals only the bronchial smooth muscle cells showed increased C3aR expression. C5aR expression also increased significantly on bronchial epithelial cells in mice treated with LPS, but was not elevated in either cell type in the OVA-challenged mice. These results demonstrate the expression of C3aR and C5aR by cells endogenous to the lung, and, given the participation of bronchial epithelial and smooth muscle cells in the pathology of diseases such as sepsis and asthma, the data suggest a role for these receptors during lung inflammation.

Topics: Aerosols; Amino Acid Sequence; Animals; Antigens, CD; Asthma; Bronchi; Cells, Cultured; Complement C3a; Complement C5a; Disease Models, Animal; Endotoxemia; Humans; Injections, Intraperitoneal; Lipopolysaccharides; Lung; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Muscle, Smooth; Muscle, Smooth, Vascular; Ovalbumin; Receptor, Anaphylatoxin C5a; Receptors, Complement; Respiratory Mucosa