Journal
BRITISH JOURNAL OF NUTRITION
Volume 111, Issue 3, Pages 452-464Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0007114513002675
Keywords
Zearalenone; Pigs; Immune responses; Liver; Signalling pathways
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Funding
- PNII - IDEI [101/2011-2014]
- PNII - PARTENERIATE [102/2012-2015]
- Romanian Ministry of Research and Technology
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Zearalenone (ZEA) is an oestrogenic mycotoxin produced by Fusarium species, considered to be a risk factor from both public health and agricultural perspectives. In the present in vivo study, a feeding trial was conducted to evaluate the in vivo effect of a ZEA-contaminated diet on immune response in young pigs. The effect of ZEA on pro-inflammatory (TNF-, IL-8, IL-6, IL-1 and interferon-) and anti-inflammatory (IL-10 and IL-4) cytokines and other molecules involved in inflammatory processes (matrix metalloproteinases (MMP)/tissue inhibitors of matrix metalloproteinases (TIMP), nuclear receptors: PPAR and NF-B1, mitogen-activated protein kinases (MAPK): mitogen-activated protein kinase kinase kinase 7 (TAK1)/mitogen-activated protein kinase 14 (p38)/mitogen-activated protein kinase 8 (JNK1)/ mitogen-activated protein kinase 9 (JNK2)) in the liver of piglets was investigated. The present results showed that a concentration of 316 parts per billion ZEA leads to a significant decrease in the levels of pro- and anti-inflammatory cytokines at both gene expression and protein levels, correlated with a decrease in the levels of other inflammatory mediators, MMP and TIMP. The results also showed that dietary ZEA induces a dramatic reduction in the expressions of NF-B1 and TAK1/p38 MAPK genes in the liver of the experimentally intoxicated piglets, and has no effect on the expression of PPAR mRNA. The present results suggest that the toxic action of ZEA begins in the upstream of the MAPK signalling pathway by the inhibition of TAK1, a MAPK/NF-B activator. In conclusion, the present study shows that ZEA alters several important parameters of the hepatic cellular immune response. From an economic point of view, these data suggest that, in pigs, ZEA is not only a powerful oestrogenic mycotoxin but also a potential hepatotoxin when administered through the oral route. Therefore, the present results represent additional data from cellular and molecular levels that could be taken into account in the determination of the regulation limit of the tolerance to ZEA.
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