casein-hydrolysate and Disease-Models--Animal

Early nutrition may influence the development of food allergies later in life. In the absence of breastfeeding, hydrolysates from cow's milk proteins (CMP) were indicated as a prevention strategy in at risk infants, but their proof of effectiveness in clinical and pre-clinical studies is still insufficient. Thanks to a validated mouse model, we then assessed specific and nonspecific preventive effects of administration of extensive hydrolysates from caseins (eHC) on the development of food allergy to CMP. The additional nonspecific effect of the probiotic. PBS pretreated mice were efficiently sensitized and demonstrated elicitation of allergic reaction after OFC, whereas mice pretreated with MPI were durably protected from allergy to CMP. eHC+/-LGG pretreatments had no protective effect on sensitization to casein (specific) or BLG (non-specific), nor on CMP-induced allergic reactions. Surprisingly, eHC+LGG mice demonstrated significantly enhanced humoral and cellular immune responses after sensitization with CMP. Only some subtle changes were evidenced by flow cytometry.. Neither specific nor nonspecific preventive effects of administration of casein-derived peptides on the development of CMP food allergy were evidenced in our experimental setup. Further studies should be conducted to delineate the mechanisms involved in the immunostimulatory potential of LGG and to clarify its significance in clinical use.

Topics: Animals; Antibodies; Caseins; Cells, Cultured; Cytokines; Disease Models, Animal; Female; Gastrointestinal Tract; Immunity, Cellular; Immunity, Humoral; Lacticaseibacillus rhamnosus; Mice, Inbred C57BL; Milk Hypersensitivity; Probiotics; Spleen; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

The aim of this study was to evaluate the antiulcerative and antinociceptive activities of milk proteins using the induced gastric ulcer with ethanol rat model and the acetic acid-induced writhing mouse model. Casein (CN), (100, 300, and 1000 mg kg

Topics: Analgesics; Animals; Caseins; Cattle; Disease Models, Animal; Gastric Mucosa; Mice; Mice, Inbred BALB C; Protein Hydrolysates; Rats; Rats, Wistar; Stomach Ulcer; Whey Proteins

The gut immune system and its modification by diet have been implicated in the pathogenesis of type 1 diabetes (T1D). Therefore, we investigated gut immune status in non-diabetes-prone LEW.1AR1 and diabetes-prone LEW.1AR1-iddm rats and evaluated the effect of a low antigen, hydrolysed casein (HC)-based diet on gut immunity and T1D. Rats were weaned onto a cereal-based or HC-based diet and monitored for T1D. Strain and dietary effects on immune homeostasis were assessed in non-diabetic rats (50-60 days old) and rats with recent-onset diabetes using flow cytometry and immunohistochemistry. Immune gene expression was analysed in mesenteric lymph nodes (MLN) and jejunum using quantitative RT-PCR and PCR arrays. T1D was prevented in LEW.1AR1-iddm rats by feeding an HC diet. Diabetic LEW.1AR1-iddm rats had fewer lymphoid tissue T cells compared with LEW.1AR1 rats. The percentage of CD4(+)  Foxp3(+) regulatory T (Treg) cells was decreased in pancreatic lymph nodes (PLN) of diabetic rats. The jejunum of 50-day LEW.1AR1-iddm rats contained fewer CD3(+) T cells, CD163(+) M2 macrophages and Foxp3(+) Treg cells. Ifng expression was increased in MLN and Foxp3 expression was decreased in the jejunum of LEW.1AR1-iddm rats; Ifng/Il4 was decreased in jejunum of LEW.1AR1-iddm rats fed HC. PCR arrays revealed decreased expression of M2-associated macrophage factors in 50-day LEW.1AR1-iddm rats. Wheat peptides stimulated T-cell proliferation and activation in MLN and PLN cells from diabetic LEW.1AR1-iddm rats. LEW.1AR1-iddm rats displayed gut immune cell deficits and decreased immunoregulatory capacity, which were partially corrected in animals fed a low antigen, protective HC diet consistent with other models of T1D.

Topics: Animals; Caseins; Cytokines; Diabetes Mellitus, Type 1; Diet; Diet, Diabetic; Digestive System; Disease Models, Animal; Edible Grain; Flow Cytometry; Gene Expression; Homeostasis; Humans; Immunity; Inflammation Mediators; Interferon-gamma; Jejunum; Macrophages; Rats, Inbred BB; Rats, Inbred Lew; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes; T-Lymphocytes, Regulatory; Weaning

Effects of intact and processed bovine milk proteins on development of chemically induced mammary tumors in female rats were compared. AIN-93G diets were made with 20% casein (CAS), casein hydrolysate (CASH), intact whey protein (IWP), or whey protein hydrolysate (WPH). Pregnant Sprague-Dawley rats were fed the diets starting at Gestational Day 4. Offspring were fed the same diet. At 50 days, female offspring (44-49/group) were gavaged with sesame oil containing 80 mg/kg of the mammary carcinogen dimethylbenzanthracene (DMBA) and euthanized 62 days posttreatment. Rats fed WPH had an adenocarcinoma incidence of 17% compared to the rats fed CAS, CASH, and IWP diets (34%, 33%, and 36% respectively) (P < 0.001). Median palpable tumor latency for rats fed WPH was greater (61 days, P < 0.001) compared to CAS (44 days), CASH (42 days) and IWP (45 days). Tumor multiplicity was also lower (1.5 vs. 3.0, P < 0.05) in rats fed WPH than in CAS and CASH fed groups. Results demonstrate that hydrolytic processing of whey protein is required for this diet to be effective in reducing DMBA-induced mammary tumors. The bioactive compounds produced during whey protein processing and mechanisms underlying the anticancer effects of WPH are yet to be identified.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Caseins; Diet; Disease Models, Animal; Female; Mammary Neoplasms, Animal; Pregnancy; Protective Agents; Protein Hydrolysates; Rats; Rats, Sprague-Dawley; Whey Proteins

The anxiolytic activity and adverse benzodiazepine-like effects of a bovine alpha s1-casein tryptic hydrolysate (CH) were evaluated. The effects of CH orally administered at doses of 5 and 15 mg/kg were compared with those of diazepam (DZ) at 3 mg/kg in the conditioned defensive burying test. Rats treated either with CH at 15 mg/kg or with DZ showed a decrease in anxiety. A drug-related difference was observed in terms of duration, as the anxiolytic-like action of CH was maintained after 7 days with twice-daily administration, whereas that of DZ was not. CH and DZ were then evaluated for their potential effects on memory in a passive avoidance paradigm. CH-treated rats had significantly longer latencies before entering the dark compartment where they were previously delivered a shock, indicating better retention relative to DZ-treated rats. In the final test, CH and DZ were evaluated for place preference, an index of the possible addictive potential of these substances. DZ-treated rats spent more time in the compartment associated with drug exposure than control rats. This effect was not found in CH-treated rats. Thus, CH did not display side effects associated with DZ, despite its affinity for gamma-aminobutyric acid(A) (GABA(A)) receptors. Specific linking of CH on GABA(A) receptor function involved in anxiolysis, but not on that implied in memory-impairing effects, may be hypothesized to explain its specific activity. This profile might render it advantageous for nutritional purposes.

Topics: Administration, Oral; Animals; Anti-Anxiety Agents; Anxiety; Avoidance Learning; Behavior, Animal; Caseins; Cattle; Diazepam; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Rats; Rats, Wistar; Receptors, GABA-A; Time Factors

Mouse experiments were conducted in order to find whether oral application of tryptic casein hydrolysate (TCH) results in enhancement of phagocytosing capacity of murine phagocytic cells as well as whether such application might be of use for prevention of inflammatory processes. Phagocytosing capacity of phagocytic cells of mice that received oral TCH once daily in a dose of 1.0 mg/g body weight dissolved in 0.5 ml of distilled water for five successive days was significantly higher (p < 0.05) than that of mice given equivalent volumes of distilled water, with a phagocytosing capacity enhancement index being 1.39 and 1.34 regarding peritoneal macrophages and blood phagocytic cells, respectively. Taken on the other hand, the immunostimulatory effects of oral TCH were found to be not enough to prevent mice from inflammation that was induced experimentally using acute (paw edema) and contact hypersensitivity models. A possibility for development of food protein enzymatic hydrolysates as antimicrobial immunostimulants acting through improvement of phagocytic cell functioning is discussed.

Topics: Administration, Oral; Animals; Carrageenan; Caseins; Dermatitis, Contact; Dinitrofluorobenzene; Disease Models, Animal; Edema; Female; Granulocytes; Inflammation; Interleukin-10; Macrophages, Peritoneal; Male; Mice; Mice, Inbred BALB C; Monocytes; Phagocytes; Phagocytosis; Trypsin; Tumor Necrosis Factor-alpha