title: Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-κB signalling molecules in pigs.
abstract: 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-α, IL-8, IL-6, IL-1β and interferon-γ) 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: PPARγ and NF-κB1, mitogen-activated protein kinases (MAPK): mitogen-activated protein kinase kinase kinase 7 (TAK1)/mitogen-activated protein kinase 14 (p38α)/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-κB1 and TAK1/p38α MAPK genes in the liver of the experimentally intoxicated piglets, and has no effect on the expression of PPARγ 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-κB 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.
authors: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov 077015, Romania.
authors: Gina Cecilia
authors: GC
authors: Pistol
authors: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov 077015, Romania.
authors: Mihail Alexandru
authors: MA
authors: Gras
authors: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov 077015, Romania.
authors: Daniela Eliza
authors: DE
authors: Marin
authors: Biotechnology Department, University of Agriculture and Veterinary Medicine, Bulevardul Marasti No. 59, Bucharest 011464, Romania.
authors: Florentina
authors: F
authors: Israel-Roming
authors: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov 077015, Romania.
authors: Mariana
authors: M
authors: Stancu
authors: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov 077015, Romania.
authors: Ionelia
authors: I
authors: Taranu
mesh_terms: D000821:Animal Feed / Q000009:adverse effects / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003433:Crosses, Genetic; D015536:Down-Regulation / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000633:toxicity; D002149:Energy Intake / Q000187:drug effects; D005506:Food Contamination; D005517:Foodborne Diseases / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020782:Matrix Metalloproteinases / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D012383:Romania; D034421:Sus scrofa; D019714:Tissue Inhibitor of Metalloproteinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014886:Weaning; D015430:Weight Gain / Q000187:drug effects; D015025:Zearalenone / Q000633:toxicity*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D015415:Biomarkers; D052244:Endocrine Disruptors; D018836:Inflammation Mediators; D020930:MAP Kinase Kinase Kinases; D020782:Matrix Metalloproteinases; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D015025:Zearalenone; D000099151:MAP Kinase Kinase Kinase 7