- UNDERSTANDING OF THE MECHANISMS WHEREBY NUTRIENTS, FOOD COMPONENTS, XENOBIOTICS AND OTHER FOOD CONTAMINANTS INTERACT WITH THE HUMAN INTESTINAL BARRIER
- UPGRADING OF UNDER-EXPLOITED FOODS (AMAZONIAN FRUITS, ANDEAN ROOTS AND TUBERS, AGRICULTURAL BY-PRODUCTS, …), WITH A SPECIFIC RICHNESS IN BIOACTIVE COMPOUNDS (POLYPHENOLS, CAROTENOIDS, GLUCOSINOLATES, …) IN THE FRAME OF FUNCTIONAL FOOD DEVELOPMENT
- TOXICOKINETICS AND EFFECTS OF ORGANIC POLLUTANTS IN MAMMALS
- IMPROVEMENT AND EVALUATION OF THE QUALITY OF COW'S MILK FATTY ACID COMPOSITION (omega-3 acids and conjugated linoleic acids - CLA)
- DETERMINATION OF THE DIETARY REQUIREMENTS OF SALMONID FISH AND IMPACT OF FEEDING STRATEGIES ON THE NUTRITIONAL QUALITY OF THEIR FLESH
- TARGETING AND TRANSPORT OF NANOPARTICLES BY M CELLS
- BIOENGINEERING OF MAMMALIAN CELLS
UNDERSANDING OF THE MECHANISMS WHEREBY NUTRIENTS, FOOD COMPONENTS, XENOBIOTICS AND OTHER FOOD CONTAMINANTS INTERACT WITH THE HUMAN INTESTINAL BARRIER
Classically, the human small intestine is the major site of absorption for nutrients. In addition, it plays the role of a strong barrier to many substances, such as xenobiotics and other food contaminants, as well as to microorganisms, particles, ... Nevertheless, it becomes increasingly evident that, in addition to these vital physiological functions, the epithelial cells lining the intestine also play a key role in biotransforming many substances entering the cells and by regulating their access to the systemic route, mainly thanks to the presence of efflux transport systems. Furthermore, an increasing piece of evidence indicates that all these proteins (enzymes, transporters and efflux pumps) are strongly regulated both at the transcriptomic and proteomic levels by the substances that are absorbed from food. Finally, toxicity is generally evaluated for one substance at a time, although, in human food, many may interact simultaneously at the level of the intestinal mucosa.
We are using a cell culture system, based on Caco-2 cells, which allows a better understanding of these topics. Recently, we have proposed that the absorption of ochratoxin A, a mycotoxin that contaminates many cereals, is limited through its excretion by an apical efflux pump, which is in turn however inhibited by some polyphenols at the concentrations physiologically encountered in the human intestine.
We have also recently described that omega-3 polyunsaturated fatty acids inhibit the expression and activity of delta9-desaturase, a key enzyme for the synthesis of unsaturated fatty acids.
In addition to studies on such interactions, we also investigate possible roles of food normal constituents or contaminants on intestinal inflammation, by examining f.i. MAPKinase and NFkappaB activation, IL8, NO and PGE2 secretions. We have also recently reported that deoxynivalenol, another food mycotoxin, activates MAPKinases and that several polyphenols inhibit NFkappaB activation and IL8 secretion.
- SERGENT, T., RIBONNET, L., KOLOSOVA, A., GARSOU, S., SCHAUT, A., DE SAEGER, S., VAN PETEGHEM, C., LARONDELLE, Y., PUSSEMIER, L., SCHNEIDER, Y-J., Molecular and cellular effects of food contaminants and secondary plant components and their plausible interactions at the intestinal level. Food and Chemical Toxicology, in press.
- ROMIER B., VAN DE WALLE J., DURING A. , LARONDELLE Y., SCHNEIDER Y.J., Modulation of signaling NF-kB activation pathway by polyphenols in human intestinal Caco-2 cells. British Journal of Nutrition, in press.
- VAN DE WALLE, J., ROMIER, B., LARONDELLE, Y., SCHNEIDER, Y-J., Influence of deoxynivalenol on NF-kB activation and IL-8 secretion in human intestinal Caco-2 cells. Toxicology Letters, in press.
- SERGENT, T., PARYS, M., GARSOU, S., PUSSEMIER, L., SCHNEIDER, Y-J., LARONDELLE, Y., Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations. Toxicology Letters, 2006, 164, 167-176.
- RINGOT, D., CHANGO, A., SCHNEIDER, Y-J., LARONDELLE, Y., Toxicokinetics and toxicodynamics of ochratoxin A, an update. Chemico-Biological Interactions, 2006, 159, 18-46.
- SERGENT, T., GARSOU, S., SCHAUT, A., DE SAEGER, S., PUSSEMIER, L., VAN PETEGHEM, C., LARONDELLE, Y., SCHNEIDER, Y-J., Differential modulation of ochratoxin A absorption across Caco-2 cells by dietary polyphenols, used at realistic intestinal concentrations. Toxicology Letters, 2005, 159, 60-70.
- BERGER, V., GABRIEL, A-F., SERGENT, T., TROUET, A., LARONDELLE, Y., SCHNEIDER, Y-J., Interaction of ochratoxin A with human intestinal CaCo-2 cells : possible implication of a multidrug resistance- associated protein (MRP2). Toxicology Letters, 2003, 140, 465-476.
UPGRADING OF UNDER-EXPLOITED FOODS (AMAZONIAN FRUITS, ANDEAN ROOTS AND TUBERS, AGRICULTURAL BY-PRODUCTS, …), WITH A SPECIFIC RICHNESS IN BIOACTIVE COMPOUNDS (POLYPHENOLS, CAROTENOIDS, GLUCOSINOLATES, …) IN THE FRAME OF FUNCTIONAL FOOD DEVELOPMENT
|Some regions of the world still possess a lot of food resources, which are only partially characterized in terms of nutrient content and health-promoting properties. In parallel, agro-industrial by-products may also become a starting material for the production of innovative food additives or ingredients. In that context, we are developing investigations with several research centres in third-world countries, as well as with industrial partners, in order to determine the nutrient composition of some promising commodities or extracts.
A special focus is put on polyphenol-rich plants from the Amazonian region and on Andean roots and tubers with the aim of associating innovation with local development.
- ANDRE, C.M., OUFIR, M., HOFFMANN, L., HAUSMAN, J-F., EVERS, D., LARONDELLE, Y., Antioxidant profiling of native Andean potato tubers (Solanum tuberosum L.) reveals cultivars with high levels of beta-carotene, alpha-tocopherol, chlorogenic acid, and petanin. Journal of Agricultural and Food Chemistry, in press.
- SOUZA, J.N.S., SILVA, E.M., LOIR, A., ROGEZ, H., REES, J-F., LARONDELLE, Y., Antioxidant capacity of four polyphenol-rich Amazonian plant extracts: a correlation study using chemical and biological in vitro assays. Food Chemistry, 2008, 106, 331-339.
- CHIRINOS, R., CAMPOS, D., COSTA, N., ARBIZU, C., PEDRESCHI, R., LARONDELLE, Y., Phenolic profiles of Andean mashua (Tropaeolum tuberosum Ruíz & Pavón) tubers: identification and evaluation of their antioxidant capacity contribution. Food chemistry, 2008, 106, 1285-1298.
SOUZA, J.N.S., SILVA, E.M., DA SILVA, M.N., ARRUDA, M.S.P., LARONDELLE, Y., ROGEZ, H., Identification and antioxidant activity of several flavonoids of Inga edulis leaves. Journal of the Brazilian Chemical Society, 2007, 18, 1276-1280.
- ANDRE, C.M., GHISLAIN, M., BERTIN, P., OUFIR, M., HERRERA, M del R., HOFFMANN, L., HAUSMAN, J-F., LARONDELLE, Y., EVERS, D., Andean potato cultivars (Solanum tuberosum L.) as a source of antioxidant and mineral micronutrients. Journal of Agricultural and Food Chemistry, 2007, 55, 366-378.
- SILVA, E.M., ROGEZ, H., LARONDELLE, Y., Optimization of extraction of phenolics from Inga edulis leaves using response surface methodology. Separation and Purification Technology, 2007, 55, 381-387.
- CHIRINOS, R., ROGEZ, H., CAMPOS, D., PEDRESCHI, R., LARONDELLE, Y., Optimization of extraction conditions of antioxidant phenolic compounds from mashua (Tropaeolum tuberosum Ruíz & Pavón) tubers. Separation and Purification Technology, 2007, 55, 217-225.
- SILVA, E.M., POMPEU, D., LARONDELLE, Y., ROGEZ, H., Optimization of the selective adsorption of polyphenols from Inga edulis leaves on macroporous resins using an experimental design methodology. Separation and Purification Technology, 2007, 53, 274-280.
- SILVA, E.M., SOUZA, J.N.S., ROGEZ, H., REES, J-F., LARONDELLE, Y., Antioxidant activities and polyphenolic contents of fifteen selected plant species from the Amazonian Region. Food chemistry, 2007, 101, 1012-1018.
- CHIRINOS, R., CAMPOS, D., ARBIZU, C., REES, J-F., ROGEZ, H., LARONDELLE, Y., NORATTO, G., CISNEROS-ZEVALLOS, L., Effect of genotype, maturity stage and post-harvest storage on phenolic compounds, carotenoid content and antioxidant capacity of Andean Mashua tubers (Tropaeolum tuberosum Ruiz & Pavón). Journal of the Science of Food and Agriculture, 2007, 87, 437-446.
- CHIRINOS, R., CAMPOS, D., BETALLELUZ, I., GIUSTI, M.M., SCHWARTZ, S.J., TIAN, Q., PEDRESCHI, R., LARONDELLE, Y., HPLC-DAD/HPLC-MS profiling of anthocyanins from Andean mashua tubers (Tropaeolum tuberosum Ruíz & Pavón) and their contribution to the overall antioxidant activity. Journal of Agricultural and Food Chemistry, 2006, 54, 7089-7097.
- ROGEZ, H., BUXANT, R., MIGNOLET, E., SOUZA, J.N.S., SILVA, E.M., LARONDELLE, Y., Chemical composition of the pulp of three typical Amazonian fruits: araça-boi (Eugenia stipitata), bacuri (Platonia insignis) and cupuaçu (Theobroma grandiflorum). European Food Research and Technology, 2004, 218, 380-384.
- RAMALLO, R., WATHELET, J-P., LE BOULENGE, E., TORRES, E., MARLIER, M., LEDENT, J-F., GUIDI, A., LARONDELLE, Y., Glucosinolates in isano (Tropaeolum tuberosum) tubers : qualitative and quantitative content and changes after maturity. Journal of the Science of Food and Agriculture, 2004, 84, 701-706.
TOXICOKINETICS AND EFFECTS OF ORGANIC POLLUTANTS IN MAMMALS
Organic pollutants (PCBs, polybrominated flame retardants, organochlorine pesticides, dioxins, etc.) have been reported to be involved in severe diseases and growth or development abnormalities. Because of their fat-soluble properties and their great persistence, they bioaccumulate in the adipose tissue of the contaminated animals. In case of fat stores mobilisation, such as during lactation, high amounts of these contaminants are transferred in the milk, presenting a potential threat for the offspring.
Lactating seals are chosen as in vivo models for these studies because females fast during the very short lactation period, while secreting an extremely fatty milk (collaborations: Dr. P.P. Pomeroy and Prof. D. Crocker).
In addition, we are developing in vitro models in collaboration with the Laboratoire de biologie animale BANI (Prof. Claude Remacle) to study the biochemical mechanisms involved in the storage and mobilisation of organic contaminants from the adipose tissue.
Through these models, we are also investigating the effects exerted by these xenobiotics on the metabolism of vitamin A.
In addition, we are starting a project focusing on the effects of PBDEs on the immune function of phocid seals. In vivo and in vitro testing will be conducted on immune cells of seals in order to investigate the mechanisms involved in the immunotoxicity of brominated flame retardants (collaboration: Dr S. Pillet and Prof. M. Fournier).
- DEBIER C., CROCKER D, HOUSER D, XHONNEUX V, THOMÉ JP. Organochlorines and lactation : mobilization and transfer to offspring in northern elephant seals, Organohalogen Compounds, 69, 2007, 833-836.
- DEBIER C, CHALON C, LE BOEUF B, DE TILLESSE T, LARONDELLE Y, THOMÉ J-P, Mobilization of PCBs from blubber to blood in Northern elephant seals (Mirounga angustirostris) during the post-weaning fast, Aquatic Toxicology, 80, 2006, 149-157.
- DEBIER C., YLITALO G.M., WEISE M., GULLAND F., COSTA D.P., LE BOEUF B.J., DE TILLESSE T., LARONDELLE Y. PCBs and DDT in the serum of juvenile California sea lions: Associations with vitamins A and E and thyroid hormones, Environ Pollut, 134, 2005, 323-332.
- DEBIER C, POMEROY P, THOMÉ J-P, MIGNOLET E, DE TILLESSE T, LARONDELLE Y, An unexpected parallelism between PCBs and vitamin A in seal milk, Aquat. Toxicol., 68, 2004, 179-183.
- DEBIER C., POMEROY P.P., DUPONT C., JOIRIS C., COMBLIN V., LE BOULENGE E., LARONDELLE Y., THOME J-P. Dynamics of PCB transfer from mother to pup during lactation in UK grey seals Halicheorus grypus: differences in PCB profile between compartments of transfer and changes during the lactation period, Mar. Ecol. Prog. Ser., 247, 2003, 249-256.
- DEBIER C, POMEROY P, DUPONT C, JOIRIS C, COMBLIN V, LE BOULENGE C,
LARONDELLE Y, THOMÉ J-P, Quantitative dynamics of PCB transfer from mother to pup during lactation in UK grey seals Halicheorus grypus, Mar. Ecol. Prog. Ser., 247, 2003, 237-248.
IMPROVEMENT AND EVALUATION OF THE QUALITY OF COW'S MILK FATTY ACID COMPOSITION (omega-3 acids and conjugated linoleic acids - CLA)
|Ruminant milk fat has been regarded as relatively undesirable in our diet, because of its high content in cholesterol and saturated fat. Interestingly however, milk fat also includes a whole set of nutrients of increasing interest for consumer's health. Moreover, the fatty acid profile of cows' milk fat is dramatically influenced by the diet of the animal.
In that context, our research aims at understanding how feeding strategies may improve the nutritional quality and some specific health-promoting properties of milk fat. A special focus is set on omega-3 fatty acids and on conjugated linoleic acids (CLA).
In parallel, our group is leading a project aiming at understanding the metabolisation of different CLA and trans-monounsaturated fatty acids isomers from milk fat in the intestinal epithelium, as well as their effects on the biochemical and physiological properties of this epithelium, with a particular focus on intestinal inflammation.
- POTTIER, J., FOCANT, M., DEBIER, C., DE BUYSSER, G., GOFFE, C., MIGNOLET, E., FROIDMONT, E. LARONDELLE, Y., Effect of Dietary Vitamin E on Rumen Biohydrogenation Pathways and Milk Fat Depression in Dairy Cows Fed High Fat Diets. Journal of Dairy Science, 2006, 89, 685-692.
- RENAVILLE, B., MULLEN, A., MOLONEY, F., LARONDELLE, Y., SCHNEIDER, Y., ROCHE, H.M., EPA and 3,10 dithia stearic acid inhibit the desaturation of trans-vaccenic acid into c9, t11-CLA through different pathways in Caco-2 and T84 cells. British Journal of Nutrition, 2006, 95, 688-695.
- DEBIER, C., POTTIER, J., GOFFE, C., LARONDELLE, Y., Present knowledge, effects of supplementation and unexpected behaviours of vitamins A and E during lactation. Livestock Production Science, 2005, 98, 135-147.
- FOCANT, M., MIGNOLET, E., MARIQUE, M., CLABOTS, F., BREYNE, T., DALEMANS, D., LARONDELLE,Y., The effect of vitamin E supplementation of cow diets containing rapeseed and linseed on the prevention of milk fat oxidation. Journal of Dairy Science, 1998, 81, 1095-1101.
DETERMINATION OF THE DIETARY REQUIREMENTS OF SALMONID FISH AND IMPACT OF FEEDING STRATEGIES ON THE NUTRITIONAL QUALITY OF THEIR FLESH
|Salmonid fish are known to rely greatly on dietary proteins for their growth. Their specific requirements in essential amino acids are however still a matter of discussion. Our team uses the facilities of the “Marcel Huet laboratory” in Louvain-la-Neuve to determine the amino acid requirements of these fish in order to optimize productivity and lower the environmental impact of fish farming.
In parallel, the research group deals with the impact of the dietary components (protein, lipid source) on the fatty acid profile and conversion in salmonids. Indeed, fish flesh fatty acid composition depends greatly both on the fatty acid profile of the feed and on the animal species, some fish species having a higher metabolisation capacity than others, with regard to fatty acid elongation, desaturation and storage.
- TRAN, T.N.T., PARKOUDA, C., DE SAEGHER, S., LARONDELLE, Y, ROLLIN, X., Comparison of the lysine utilization efficiency in different plant protein sources supplemented with L-lysine.HCl in rainbow trout (Oncorhynchus mykiss) fry. Aquaculture, 2007, 272, 477-488.
- ABBOUDI, T., OOGHE, W., LARONDELLE, Y., ROLLIN, X., Determination of the threonine requirement for maintenance in Atlantic salmon (Salmo salar L.) fry with the diet dilution procedure. Aquaculture Nutrition, 2007, 13, 281-290.
- ABBOUDI, T., MAMBRINI, M., OOGHE, W., LARONDELLE, Y., ROLLIN, X., Protein and Lysine requirements for maintenance and for tissue accretion in Atlantic salmon (Salmo salar) fry. Aquaculture, 2006, 261, 369-383.
- ROLLIN, X., WAUTERS, J-B., BODIN, N., LARONDELLE, Y., OOGHE, W., WATHELET, B., ABBOUDI, T., Maintenance threonine requirement and efficiency of its use for accretion of whole-body threonine and protein in Atlantic salmon , (Salmo salar L.) fry. British Journal of Nutrition, 2006, 95, 234-245.
- ROLLIN, X., MAMBRINI, M., ABBOUDI, T., LARONDELLE, Y., KAUSHIK, S., The optimum dietary indispensable amino acid pattern for growing Atlantic salmon (Salmo salar L.) fry. British Journal of Nutrition, 2003, 90, 865-876.
- ROLLIN, X., PENG, J., PHAM, D., ACKMAN, R.G., LARONDELLE, Y., The effect of dietary lipid and strain difference on polyunsaturated fatty acid composition and conversion in anadromous and landlocked Atlantic salmon (Salmo salar L.) parr. Comparative Biochemistry and Physiology Part B, 2003, 134, 349-366.
- PENG, J., LARONDELLE, Y, PHAM, D., ACKMAN, R.G., ROLLIN, X., Polyunsaturated fatty acid profiles of whole body phospholipids and triacylglycerols in anadromous and landlocked Atlantic salmon (Salmo salar L.) fry. Comparative Biochemistry and Physiology Part B, 2003, 134, 335-348.
TARGETING AND TRANSPORT OF NANOPARTICLES BY M CELLS
Although the intestine acts as a selective barrier for xenobiotics (see above), it also allows the entry of nanoparticles and microorganisms, which is a key element in the regulation of immunity. Better understanding these transport mechanisms could obviously help to better deliver some very active peptidic drugs or mucosal vaccines.
- V. PREAT (UCL-School of Pharmacy): joint supervision of the program
- C. JEROME (ULg): synthesis of new polymers
- J. MARCHAND (UCL-ISV): synthesis of peptidomimetics.
- DES RIEUX A., M. GARINOT, V. FIEVEZ, Y.-J. SCHNEIDER and V. PREAT (2006).
Nanoparticles as potential oral delivery systems of proteins and vaccines.
J. Contr. Rel., 116, 1-27.
- DES RIEUX A., V. FIEVEZ, V. THEATE, I. MAST J.J.MAST,, V. PREAT and Y.-J. SCHNEIDER (2007).
An improved in vitro model of human intestinal follicle-associated epithelium to study nanoparticle transport by M cells.
Eur. J. Pharm. Sci., 30, 380-91.
- DES RIEUX A., V. FIEVEZ, M. MOMTAZ, C. DETREMBLEUR, M. ALONSO-SANDE, J. VAN GELDER, A. CAUVIN, Y.-J. SCHNEIDER and V. PREAT (2007).
Influence of M cells on oral delivery of helodermin.
J. Contr. Rel., 118, 294-302.
- GARINOT M., FIEVEZ V., POURCELLE V., STOFFELBACH F., DES RIEUX A., PLAPIED L., THEATE I., FREICHELS H., JEROME C., MARCHAND-BRYNAERT J., SCHNEIDER Y.-J., PREAT V. (2007)
PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination.
J. Contr. Rel., 120,195-204.
- des Rieux A, Fievez V, Momtaz M, Detrembleur C, Alonso-Sande M, Van Gelder J, Cauvin A, Schneider YJ, Préat V.
Helodermin-loaded nanoparticles: characterization and transport across an in vitro model of the follicle-associated epithelium.
J Control Release. 2007 Apr 23;118(3):294-302.
- Mathot F, des Rieux A, Ariën A, Schneider YJ, Brewster M, Préat V.
Transport mechanisms of mmePEG(750)P(CL-co-TMC) polymeric micelles across the intestinal barrier.
J Control Release. 2007 Dec 20;124(3):134-43.
BIOENGINEERING OF MAMMALIAN CELLS
Among the different expression vectors, mammalian cells are currently among the most used in biotechnology. They are indeed able to perform sophisticated post-translational modifications and to secrete glycoproteins identical or, at least, very similar to human ones. Nevertheless, the physiology of the mammalian cell in the bioreactor remains very poorly understood. Furthermore, for both biosafety and downstream processing reasons, the cell environment must be increasingly defined and devoid of any constituents from animal origin. Therefore, hydrolysates of vegetal proteins (peptones) are increasingly used to substitute animal serum and supplement chemically defined nutritive media.
- S. AGATHOS (UCL-ISV): cell bioengineering
G. BASTIN (UCL-Cesame): modeling.
Key publications :
- BURTEAU CC, VERHOEYE FR, MOLS JF, BALLEZ J-S, AGATHOS SN, SCHNEIDER Y-J, Fortification of a protein-free cell culture medium with plant peptones improves cultivation and productivity of an interferon-# producing CHO cell line, In Vitro Cell. Dev. Biol.-Animal, 39, 2003, 291-296.
- MOLS J, PEETERS-JORIS C, AGATHOS SN, SCHNEIDER Y-J, Origin of rice protein hydrolysates added to protein-free media alters secretion and extracellular proteolysis of recombinant interferon-# as well as CHO-320 cell growth, Biotechnol. Lett. 26, 2004, 1043-1046.
- MOLS J, PEETERS-JORIS C, WATTIEZ R, AGATHOS S, SCHNEIDER Y-J, Recombinant interferon-gamma secreted by CHO-320 cells cultivated in suspension in protein-free media is protected against extracellular proteolysis by the expression of natural protease inhibitors and by the addition of plant protein hydrolysates to the culture medium, In Vitro Cell. Dev. Biol.-Animal, 41, 2005, 83-91..
- PROVOST A, BASTIN G, AGATHOS SN, SCHNEIDER Y-J, Metabolic Design of Macroscopic Models: Application to CHO cells, Bioproc. Biosys. Eng., in press.