Project Details
Projekt
Oral deoxynivalenol exposure of pigs modulates the pathophysiological impact of a subsequent LPS-stimulus
Subject Area
Animal Breeding, Animal Nutrition, Animal Husbandry
Term
from 2002 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5374972
In the completed project period we were able to demonstrate the detrimental effect of deoxynivalenol (DON) and lipopolysaccharide (LPS) on the in vivo protein synthesis as well as the intestinal barrier integrity in vivo and in vitro. The interaction of DON and LPS and its impact on the acute phase reaction (APR), their related cytokine expression and the subsequently induced pathophysiological effects, in particular on intestinal and hepatic tissue and immune cells, depended primarily on their route of application. LPS-induced pathohistological lesions such as haemorrhage and lymphocyte infiltration in the liver seemed to be ameliorated in pigs received a diet containing DON 5 weeks prior to LPS challenge. However, the contribution of the liver, an immunologically active organ (LPS-clearance, mediation of APR), to metabolisation and elimination of DON (conjugation, biliary excretion) could not be investigated in depth due to the fact that only peripheral venous blood was obtainable in the previous experimental setup. In order to estimate the portal influx of DON and LPS from the gastrointestinal tract (GIT) their time-dependent concentrations in the portal vein are essential. Moreover, determining orally administered trans- and paracellular markers (e.g. PEG) in the portal blood would enable an estimation of the intestinal epithelial permeability and thus of intestinal barrier integrity in vivo. Our investigations (in vitro and in vivo) demonstrated that the intestinal lining is more vulnerable to basolateral (i.e. systemic) exposure to toxins as compared to the apical side, thus knowledge of the actual arterial influx of DON and LPS to the GIT in vivo is crucial. In vitro trials we could show a significant regulation of genes (microarray) related to energy metabolism, transcription, translation as well as cell communication when porcine intestinal epithelial cells were exposed to basolateral DON whereas apical exposure of the same concentration yielded no changes. It is essential to investigate whether these changes found on a mRNA-level are reflected in their corresponding structure and function in vitro and whether this holds also true for the intestinal epithelium in vivo.Our objectives in the present project proposal are to contribute to the elucidation of the mechanisms underlying DON-associated modulation of a subsequent LPS stimulus in an advanced animal model. Particularly we will focus on the integrated action of intestinal barrier and liver in toxin absorption and metabolisation as well as on the systemic inflammatory response, reflected in the immune cell population in local and peripheral immune system.
DFG Programme
Research Grants
Participating Person
Dr. Jeannette Klüß
