The Effects and Mechanisms of Action of Zearalenone in Human Intestinal Epithelial Cells

Abstract Fusariotoxins are fungal secondary metabolites produced mainly by Fusarium and Giberella species, zearalenone (ZEA) being one of the most widespread members of this class. Exposure to ZEA affects the health of animals and humans, predominantly by disrupting the activity of the reproductive system due to its structural resemblance to estrogen, but it also affects other systems such as the digestive, nervous and immune systems. The main route through which ZEA enters the body is by ingestion, the intestinal epithelium being the first tissue exposed to the toxin. The intestinal barrier not only has a mechanical role in defending the body, it is also able to secrete effector molecules involved in the immune and inflammatory response such as cytokines. In this in vitro study, performed on the line Caco-2, the effects of ZEA on inflammation of the intestinal epithelium were studied by quantifying gene expression and protein concentration of pro-inflammatory cytokines IL-1β, TNF-α, IL-6 and IL-8. Also, the mechanism of inflammation that ZEA can affect at intestinal level was investigated by monitoring the level of mRNA and the protein expression of the nuclear receptors NF-κB and Nrf-2. The results of this study demonstrate that ZEA has an anti-inflammatory character on human intestinal epithelial cells Caco-2, reducing the gene expression of the pro-inflammatory cytokines IL-1β, TNF-α, IL-6, IL-8. Also, ZEA led to a decrease in the protein concentration of IL-6 and IL-8. The anti-inflammatory response seems to be induced by modulation of gene and protein expresion of NF-κB and Nrf-2 nuclear receptors.