Effect of Fusarium-Derived Metabolites on the Barrier Integrity of Differentiated Intestinal Porcine Epithelial Cells (IPEC-J2)

Abstract

The human, animal and plant pathogen Fusarium, which contaminates agricultural commodities worldwide, produces numerous secondary metabolites. An example is the thoroughly-investigated deoxynivalenol (DON), which severely impairs gastrointestinal barrier integrity. However, to date, the toxicological profile of other Fusarium-derived metabolites, such as enniatins, beauvericin, moniliformin, apicidin, aurofusarin, rubrofusarin, equisetin and bikaverin, are poorly characterized. Thus we examined their effects—as metabolites alone and as metabolites in combination with DON—on the intestinal barrier function of differentiated intestinal porcine epithelial cells (IPEC-J2) over 72 h. Transepithelial electrical resistance (TEER) was measured at 24-h intervals, followed by evaluation of cell viability using neutral red (NR) assay. Enniatins A, A1, B and B1, apicidin, aurofusarin and beauvericin significantly reduced TEER. Moniliformin, equisetin, bikaverin and rubrofusarin had no effect on TEER. In the case of apicidin, aurofusarin and beauvericin, TEER reductions were further substantiated by the addition of otherwise no-effect DON concentrations. In all cases, viability was unaffected, confirming that TEER reductions were not due to compromised viability. Considering the prevalence of mycotoxin contamination and the diseases associated with intestinal barrier disruption, consumption of contaminated food or feed may have substantial health implications.

Emerging Fusarium and Alternaria Mycotoxins: Occurrence, Toxicity and Toxicokinetics

“…BEA caused cell cycle arrest in the G2/M phase and S phase, presumably as a result of the cellular redox imbalance and at higher concentrations (12 µM), BEA caused DNA damage in Caco-2 cells. Above, 2.5–10 µM BEA promoted chromosome aberrations, increased the frequency of sister-chromatid exchanges and induced micronuclei in human lymphocytes ( Table 2 ) [ 5 , 6 , 7 , 59 ].…”

“…In addition, ENNs and BEA reduced the intestinal barrier integrity in vitro. Reduced intestinal barrier integrity could not only affect bioavailability of xenobiotics, but could also increase the susceptibility to diseases and reduce performance [ 59 , 89 ]. Taken together, the toxicokinetic behavior of these mycotoxins may be complex and can vary between both individuals and species, making species- and compound-specific studies essential.…”

“…MON did not affect intestinal nor blood capillary integrity in vitro. However, in vitro studies suggest that the molecule can pass the blood brain barrier [ 59 , 106 ]. After single oral gavage, 42% of the administered MON was excreted in the urine of rats within 24 h post administration, and less than 1% was excreted in the feces.…”

Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate?

“…Most of the recent studies used mathematical modelling according to Bliss or/and Loewe (or some modified Loewe's method) for assessing the nature of the effect of combination of mycotoxins. However several in vitro studies assed mycotoxin combined effects comparing the effect of combination to the effect of single mycotoxin [70][71][72] or only to negative controls [73][74][75][76] without estimating the theoretical (expected) effect of the combination (Table 3). Conclusions based on those studies are unreliable because the question of the nature of interaction of combination has not even been asked in a scientific manner to get a clear and exact answer.…”

Cytotoxic and Antitumoral Effects of Bikaverin from Gibberella fujikuroi on L5178Y Lymphoma Murine Model

“…For this reason, the inhibition of CK2 is important to induce the physiological process of apoptosis, leading to tumor cell death [26]. In addition, bikaverin was not genotoxic and cytotoxic in primary rat hepatocytes at low concentrations (˂100µM) and had not affect the cell viability on differentiated intestinal porcine epithelial cells (IPEC-J2) at 5-10 µM [27,28].…”