The gastrointestinal tract is the first target for the potentially harmful effects of mycotoxins after intake of mycotoxin contaminated food or feed. With deoxynivalenol (DON), T-2 toxin (T-2), fumonisin B1 (FB1) and zearalenone (ZEA) being important Fusarium toxins in the northern hemisphere, this study aimed to investigate in vitro the toxic effect of these mycotoxins on intestinal porcine epithelial cells derived from the jejunum (IPEC-J2 cells). Viability of IPEC-J2 cells as well as the proportion of apoptotic and necrotic IPEC-J2 cells was determined by flow cytometry after 72 h of exposure to the toxins. Correlatively, the integrity of the intestinal epithelial cell monolayer was studied using Transwell® inserts, in which the trans-epithelial electrical resistance (TEER) and passage of the antibiotics doxycycline and paromomycin were used as endpoints. We demonstrated that the percentage of Annexin-V-FITC and PI negative (viable) cells, Annexin-V-FITC positive and PI negative (apoptotic) cells and Annexin-V-FITC and PI positive (necrotic) IPEC-J2 cells showed a mycotoxin concentration-dependent relationship with T-2 toxin being the most toxic. Moreover, the ratio between Annexin-V-FITC positive and PI negative cells and Annexin-V-FITC and PI positive cells varied depending on the type of toxin. More Annexin-V-FITC and PI positive cells could be found after treatment with T-2 toxin, while more Annexin-V-FITC positive and PI negative cells were found after exposure to DON. Consistent with the cytotoxicity results, both DON and T-2 decreased TEER and increased cellular permeability to doxycycline and paromomycin in a time- and concentration-dependent manner. It was concluded that Fusarium mycotoxins may severely disturb the intestinal epithelial barrier and promote passage of antibiotics.

The mycotoxin T-2 toxin and Salmonella Typhimurium infections pose a significant threat to human and animal health. Interactions between both agents may result in a different outcome of the infection. Therefore, the aim of the presented study was to investigate the effects of low and relevant concentrations of T-2 toxin on the course of a Salmonella Typhimurium infection in pigs. We showed that the presence of 15 and 83 μg T-2 toxin per kg feed significantly decreased the amount of Salmonella Typhimurium bacteria present in the cecum contents, and a tendency to a reduced colonization of the jejunum, ileum, cecum, colon and colon contents was noticed. In vitro, proteomic analysis of porcine enterocytes revealed that a very low concentration of T-2 toxin (5 ng/mL) affects the protein expression of mitochondrial, endoplasmatic reticulum and cytoskeleton associated proteins, proteins involved in protein synthesis and folding, RNA synthesis, mitogen-activated protein kinase signaling and regulatory processes. Similarly low concentrations (1-100 ng/mL) promoted the susceptibility of porcine macrophages and intestinal epithelial cells to Salmonella Typhimurium invasion, in a SPI-1 independent manner. Furthermore, T-2 toxin (1-5 ng/mL) promoted the translocation of Salmonella Typhimurium over an intestinal porcine epithelial cell monolayer. Although these findings may seem in favour of Salmonella Typhimurium, microarray analysis showed that T-2 toxin (5 ng/mL) causes an intoxication of Salmonella Typhimurium, represented by a reduced motility and a downregulation of metabolic and Salmonella Pathogenicity Island 1 genes. This study demonstrates marked interactions of T-2 toxin with Salmonella Typhimurium pathogenesis, resulting in bacterial intoxication.

It is recognized that mycotoxins can cause a variety of adverse health effects in animals, including altered gastrointestinal barrier function. It is the aim of the present study to determine whether mycotoxin-contaminated diets can alter the oral bioavailability of the antibiotics doxycycline and paromomycin in pigs, and whether a mycotoxin adsorbing agent included into diets interacts with those antibiotics. Experiments were conducted with pigs utilizing diets that contained blank feed, mycotoxin-contaminated feed (T-2 toxin or deoxynivalenol), mycotoxin-contaminated feed supplemented with a glucomannan mycotoxin binder, or blank feed supplemented with mycotoxin binder. Diets with T-2 toxin and binder or deoxynivalenol and binder induced increased plasma concentrations of doxycycline administered as single bolus in pigs compared to diets containing blank feed. These results suggest that complex interactions may occur between mycotoxins, mycotoxin binders, and antibiotics which could alter antibiotic bioavailability. This could have consequences for animal toxicity, withdrawal time for oral antibiotics, or public health.

Abrupt deprivation of substrates to neuronal tissue triggers a number of pathological events (the "ischemic cascade") that lead to cell death. As this is a process of delayed neuronal cell death and not an instantaneous event, several pharmacological and non-pharmacological strategies have been developed to attenuate or block this cascade. The most promising neuroprotectant so far is therapeutic hypothermia and its beneficial effects have inspired researchers to further improve its protective benefit by combining it with other neuroprotective agents. This review provides an overview of all neuroprotective strategies that have been combined with therapeutic hypothermia in rodent models of focal cerebral ischemia. A distinction is made between drugs interrupting only one event of the ischemic cascade from those mitigating different pathways and having multimodal effects. Also the combination of therapeutic hypothermia with hemicraniectomy, gene therapy and protein therapy is briefly discussed. Furthermore, those combinations that have been studied in a clinical setting are also reviewed.