interleukin-8 and zearalenol

Zearalenone (ZEA), a mycotoxin produced by several Fusarium spp., is most commonly found as a contaminant in stored grain. ZEA derivatives (α-zearalenol (α-ZOL), β-zearalenol (β-ZOL)) can also be produced by Fusarium spp. in corn stems infected by fungi in the field. Also, following oral exposure, zearalenone is metabolized in various tissues, particularly in the liver, the major metabolites being α-ZOL and β-ZOL. The co-exposure of cells to mixture of a combination of mycotoxins may cause an increase of toxicity produced by these mycotoxins. In this in vitro study, we investigated the combined effects of ZEA, α-ZOL, β-ZOL in binary mixtures on the viability and inflammatory response of human liver cancer cell line (HepG2). Cell viability was assessed after 72 h using a neutral red assay. Effect of the toxins and their binary combinations on the expression of genes involved in inflammation (IL-1β, TNF-α, and IL-8) were assessed through qPCR. Our viability data showed that irrespective of the toxin combinations, the toxins have synergistic effect. ZEA + α-ZOL and ZEA + β-ZOL mixtures have induced a slight to high antagonistic response on inflammatory cytokines at low concentrations that have turned into strong synergism for high concentrations. α-ZOL + β-ZOL showed antagonistic effects on inflammation for IL-1β and TNF-α, but act synergic for IL-8 at high toxin concentrations. This study clearly shows that co-contamination of food and feed with ZEA metabolites should be taken into consideration, as the co-exposure to mycotoxins might result in stronger adverse effect than resulted from the exposure to individual toxin.

Topics: Cell Survival; Cytokines; Drug Interactions; Gene Expression Regulation; Hep G2 Cells; Humans; Inflammation; Interleukin-1beta; Interleukin-8; Mycotoxins; Tumor Necrosis Factor-alpha; Zearalenone; Zeranol

The intestinal epithelium is the first barrier against food contaminants. Zearalenone (ZEN) is an estrogenic mycotoxin that was identified as a common contaminant of cereal grains and food and feedstuffs. In the present study, we have investigated the in vitro effects of ZEN and some of its metabolites (α-ZOL, β-ZOL) in concentrations of 10-100 µM on a swine epithelial cell line: Intestinal porcine epithelial cells (IPEC-1). We demonstrated that both ZEN metabolites were more toxic for IPEC cells as resulted from the XTT test, while for doses lower than 10 µM, only β-ZOL showed a more pronounced cytotoxicity versus epithelial cells as resulted from neutral red assay. ZEN has no effect on TER values, while α-ZOL significantly decreased the TER values, starting with day 4 of treatment. β-ZOL had a dual effect, firstly it induced a significant increase of TER, and then, starting on day 6, it induced a dramatic decrease of TER values as compared with on day 0. Concerning the cytokine synthesis, our results showed that ZEN has a tendency to increase the synthesis of IL-8 and IL-10. By contrast, α- and β-ZOL decreased the expression of both IL-8 and IL-10, in a dose dependent manner. In conclusion, our results showed that ZEN and its metabolites differently affected porcine intestinal cell viability, transepithelial resistance and cytokine synthesis with important implication for gut health.

Topics: Animals; Cell Line; Cell Survival; Epithelial Cells; Estrogens, Non-Steroidal; Food Contamination; Interleukin-10; Interleukin-8; Intestinal Mucosa; Swine; Zearalenone; Zeranol