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

British Journal of Nutrition - Tập 111 Số 3 - Trang 452-464 - 2014
Gina Cecilia Pistol1, Mihail Alexandru Gras1, Daniela Eliza Marin1, Florentina Israel-Roming2, Mariana Stancu1, Ionelia Țăranu1
1Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov077015, Romania
2Biotechnology Department, University of Agriculture and Veterinary Medicine, Bulevardul Marasti No. 59, Bucharest011464, Romania

Tóm tắt

Zearalenone (ZEA) is an oestrogenic mycotoxin produced byFusariumspecies, considered to be a risk factor from both public health and agricultural perspectives. In the presentin vivostudy, a feeding trial was conducted to evaluate thein vivoeffect 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 ofNF-κB1andTAK1/p38αMAPK genes in the liver of the experimentally intoxicated piglets, and has no effect on the expression ofPPARγmRNA. 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.

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Tài liệu tham khảo

10.1016/S0300-483X(03)00329-9

10.1002/mnfr.200500191

10.1016/j.vetimm.2005.06.016

Stec, 2009, Effects of aflatoxin B1, ochratoxin A, patulin, citrinin, and zearalenone on the in vitro proliferation of pig blood lymphocytes, Bull Vet Inst Pulawy, 53, 129

10.1080/02652030601053626

10.1016/j.fct.2008.01.023

10.1093/toxsci/kfp117

10.4315/0362-028X-72.3.662

10.1051/vetres/2009023

10.1016/0041-0101(96)00008-6

CCFAC (2000) Codex Committee on Food Additives and Contaminants. Posting Date. Joint FAO/WHO Expert Committee on Food Additives: Position Paper on Zearalenone. Publication CCFAC 00/19. Rome: Codex Alimentarius Commission.

10.1016/j.taap.2008.03.016

10.1006/taap.1995.1132

10.1016/j.anireprosci.2010.10.002

10.1007/s12550-010-0053-8

10.1016/j.ijfoodmicro.2007.07.019

10.1128/CMR.16.3.497-516.2003

10.1017/S0007114511000341

10.1016/j.tiv.2003.12.011

10.1016/j.tox.2010.11.006

10.1111/j.1600-0773.1978.tb02267.x

10.1093/toxsci/kfj163

10.1164/rccm.200909-1350OC

10.1016/S1383-5718(03)00093-7

10.1016/j.toxicon.2008.04.162

10.1111/j.1439-0396.2005.00516.x

10.1084/jem.183.4.1829

10.1093/toxsci/kfs239

2004, Opinion of the Scientific Panel on contaminants in the food chain on a request from the commission related to zearalenone as undesirable substance in animal feed, EFSA J, 89, 1

10.1016/j.bcp.2012.02.007

MacDonald, 2005, Determination of zearalenone in barley, maize and wheat flour, polenta, and maize-based baby food by immunoaffinity column cleanup with liquid chromatography: interlaboratory study, AOAC Int, 88, 1733, 10.1093/jaoac/88.6.1733

10.1074/jbc.M207453200

10.1006/meth.2001.1262

10.2527/jas.2006-524

10.2903/j.efsa.2011.2197

JECFA (2000) Zearalenone. In: Safety Evaluation of Certain Food Additives and Contaminants. WHO/FAO Food Additives Series 44 [Joint FAO/WHO Expert Committee on Food Additives, editor]. Geneva: WHO (IPCS – International Programme on Chemical Safety).

10.1093/toxsci/kfi225

10.1111/j.1582-4934.2007.00022.x

10.1016/j.toxicon.2010.06.020

10.1097/01.CCM.0000124876.31138.F6

10.1371/journal.pone.0060374

10.1210/endo.139.10.6216

10.2527/jas.2007-0177

10.1093/toxsci/kfl012

10.1016/j.tiv.2007.01.001

10.1016/j.tox.2006.06.004

10.1124/mol.61.5.997

1982, Carcinogenesis Bioassay of Zearalenone in F 344/N Rats and F6C3F1 Mice. National Toxicology Program Technical Report Series no. 235

10.1002/jbt.20284

Ninomiya-Tsuji, 1999, The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway, Nature, 398, 252, 10.1038/18465

10.1051/vetres:2008043

10.1016/0273-2300(87)90037-7

10.1152/ajpcell.00470.2006

10.1016/j.fct.2008.05.016

10.2527/jas.2010-3658

10.1016/j.taap.2012.01.016

10.1016/S0378-4274(01)00312-5

10.1211/jpp.61.11.0015

10.1172/JCI26283

10.1126/science.1072682

10.1016/j.intimp.2010.09.017

10.7164/antibiotics.56.337

10.1016/0378-4274(84)90129-2

10.1016/j.tiv.2011.07.002

10.1002/(SICI)1096-9896(199910)189:2<265::AID-PATH415>3.0.CO;2-#

10.1038/sj.onc.1210392

Lapierre, 2007, The liver: an organ of the immune system?, Med Sci, 23, 985

10.1016/j.imbio.2008.07.015

10.1211/jpp.60.6.0012

10.1016/j.reprotox.2004.08.005

10.1186/1471-2164-8-215

Gesslein, 2010, Mitogen-activated protein kinases in the porcine retinal arteries and neuroretina following retinal ischemia–reperfusion, Mol Vis, 16, 392

Primer 3. http://frodo.wi.mit.edu/cgi-bin/primer3/primer3_www.cgi (accessed May 2012).

10.1016/j.vetimm.2004.09.018

10.1016/j.tiv.2011.06.022

Wang YC, Deng JL, Xu SW, et al. (2012) Effects of zearalenone on IL-2, IL-6, and IFN-γ mRNA levels in the splenic lymphocytes of chickens. ScientificWorldJournal, 2012 (article ID 567327).

10.1016/j.tox.2004.08.020

10.1038/35154

10.1016/j.mrgentox.2003.09.009

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Thông tin xuất bản

British Journal of Nutrition

Tập 111 Số 3

452-464

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