脱氧雪腐镰刀菌烯醇对猪毒害作用及毒理机制研究进展

doi:10.11843/j.issn.0366-6964.2023.01.003

摘要/Abstract

摘要： 脱氧雪腐镰刀菌烯醇(deoxynivalenol,DON)是一种常见的污染粮食、饲料和食品的霉菌毒素，严重影响人和牲畜的健康。猪对DON非常敏感，DON可造成猪拒食、生长抑制、呕吐以及器官损伤、细胞毒性、免疫毒性等毒害作用。本文主要综述了DON对猪的毒害作用、毒理机制以及解毒剂开发等方面的研究进展，尤其关注DON毒理作用的遗传调控研究，旨在为从遗传本质提高猪对脱氧雪腐镰刀菌烯醇的抵抗力提供更全面的参考。

关键词: 猪, 脱氧雪腐镰刀菌烯醇, 毒害作用, 毒理机制, 解毒剂, 遗传调控

Abstract: Deoxynivalenol (DON), is one of the common mycotoxins that contaminate grain, feed and food, which seriously affects the health of humans and livestock. Pigs are very sensitive to DON, which can cause toxic effects such as antifeeding, growth inhibition, vomiting, organ damage, cytotoxicity, and immunotoxicity to pigs. The toxic effects, toxicological mechanisms and antidote development of DON on pigs were reviewed in this paper. Specially, the genetic regulation of the toxicological effects of DON was concerned, which aimed to provide more comprehensive references for improving the resistance of pigs to deoxynivalenol from genetic nature.

Key words: pig, deoxynivalenol, toxic effect, toxicological mechanism, antidote, genetic regulation

中图分类号:

S859.8

戴超辉, 李辉, 赵为民, 付言峰, 廖超, 李碧侠, 王学敏, 程金花. 脱氧雪腐镰刀菌烯醇对猪毒害作用及毒理机制研究进展[J]. 畜牧兽医学报, 2023, 54(1): 24-35.

DAI Chaohui, LI Hui, ZHAO Weimin, FU Yanfeng, LIAO Chao, LI Bixia, WANG Xuemin, CHENG Jinhua. Research Progress in Toxic Effect of Deoxynivalenol on Pigs and Its Toxicological Mechanism[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(1): 24-35.

参考文献 86

[1]	KHOSHAL A K,NOVAK B,MARTIN P G P,et al.Co-occurrence of DON and emerging mycotoxins in worldwide finished pig feed and their combined toxicity in intestinal cells[J].Toxins (Basel),2019,11(12):727.
[2]	STREIT E,NAEHRER K,RODRIGUES I,et al.Mycotoxin occurrence in feed and feed raw materials worldwide:long-term analysis with special focus on Europe and Asia[J].J Sci Food Agric,2013,93(12):2892-2899.
[3]	GRUBER-DORNINGER C,JENKINS T,SCHATZMAYR G.Global mycotoxin occurrence in feed:a ten-year survey[J].Toxins (Basel),2019,11(7):375.
[4]	GLENN A E.Mycotoxigenic Fusarium species in animal feed[J].Anim Feed Sci Technol,2007,137(3-4):213-240.
[5]	林少青,董斌.脱氧雪腐镰刀菌烯醇的免疫毒性研究进展[J].广东饲料,2009,18(7):43-45.LIN S Q,DONG B.Research progress on immune toxicity of deoxynivalenol[J].Guangdong Feed,2009,18(7):43-45.(in Chinese)
[6]	LI Y T,HWANG S G,HUANG Y M,et al.Effects of Trichoderma asperellum on nutrient uptake and Fusarium wilt of tomato[J]. Crop Prot,2018,110:275-282.
[7]	张升,张伟,王丽,等.氨基酸态氮对禾谷镰刀菌生长及DON毒素产生的影响[J].江苏农业学报,2020, 36(6):1403-1410.ZHANG S,ZHANG W,WANG L,et al.Effects of amino acid nitrogen on the growth of Fusarium graminearum and DON toxin production[J].Jiangsu Journal of Agricultural Sciences,2020,36(6):1403-1410.(in Chinese)
[8]	PRONYK C,CENKOWSKI S,ABRAMSON D.Superheated steam reduction of deoxynivalenol in naturally contaminated wheat kernels[J].Food Control,2006,17(10):789-796.
[9]	PRELUSKY D B,GERDES R G,UNDERHILL K L,et al.Effects of low-level dietary deoxynivalenol on haematological and clinical parameters of the pig[J].Nat Toxins,1994,2(3):97-104.
[10]	PESTKA J J,SMOLINSKI A T.Deoxynivalenol:toxicology and potential effects on humans[J].J Toxicol Environ Health B Crit Rev,2005,8(1):39-69.
[11]	HOLANDA D M,KIM S W.Mycotoxin occurrence,toxicity,and detoxifying agents in pig production with an emphasis on deoxynivalenol[J].Toxins (Basel),2021,13(2):171.
[12]	HOOFT J M,BUREAU D P.Deoxynivalenol:mechanisms of action and its effects on various terrestrial and aquatic species[J]. Food Chem Toxicol,2021,157:112616.
[13]	DERSJANT-LI Y,VERSTEGEN M W A,GERRITS W J J.The impact of low concentrations of aflatoxin,deoxynivalenol or fumonisin in diets on growing pigs and poultry[J].Nutr Res Rev,2003,16(2):223-239.
[14]	MARIN S,RAMOS A J,CANO-SANCHO G,et al.Mycotoxins:occurrence,toxicology,and exposure assessment[J].Food Chem Toxicol,2013,60:218-237.
[15]	FLANNERY B M,CLARK E S,PESTKA J J.Anorexia induction by the trichothecene deoxynivalenol (vomitoxin) is mediated by the release of the gut satiety hormone peptide YY[J].Toxicol Sci,2012,130(2):289-297.
[16]	PESTKA J J.Deoxynivalenol:mechanisms of action,human exposure,and toxicological relevance[J].Arch Toxicol,2010,84(9):663-679.
[17]	PRELUSKY D B,TRENHOLM H L.The efficacy of various classes of anti-emetics in preventing deoxynivalenol-induced vomiting in swine[J].Nat Toxins,1993,1(5):296-302.
[18]	PINTON P,BRAICU C,NOUGAYREDE J P,et al.Deoxynivalenol impairs porcine intestinal barrier function and decreases the protein expression of claudin-4 through a mitogen-activated protein kinase-dependent mechanism[J].J Nutr,2010,140(11):1956-1962.
[19]	HOLANDA D M,YIANNIKOURIS A,KIM S W.Investigation of the efficacy of a postbiotic yeast cell wall-based blend on newly-weaned pigs under a dietary challenge of multiple mycotoxins with emphasis on deoxynivalenol[J].Toxins (Basel), 2020,12(8):504.
[20]	HALAWA A,DÄNICKE S,KERSTEN S,et al.Effects of deoxynivalenol and lipopolysaccharide on electrophysiological parameters in growing pigs[J].Mycotoxin Res,2012,28(4):243-252.
[21]	GOYARTS T,DÄNICKE S,BRüSSOW K P,et al.On the transfer of the Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) from sows to their fetuses during days 35-70 of gestation[J].Toxicol Lett,2007,171(1-2):38-49.
[22]	BERGSJØ B,LANGSETH W,NAFSTAD I,et al.The effects of naturally deoxynivalenol-contaminated oats on the clinical condition,blood parameters,performance and carcass composition of growing pigs[J].Vet Res Commun,1993,17(4):283-294.
[23]	MIKAMI O,YAMAMOTO S,YAMANAKA N,et al.Porcine hepatocyte apoptosis and reduction of albumin secretion induced by deoxynivalenol[J].Toxicology,2004,204(2-3):241-249.
[24]	MIKAMI O,YAMAGUCHI H,MURATA H,et al.Induction of apoptotic lesions in liver and lymphoid tissues and modulation of cytokine mRNA expression by acute exposure to deoxynivalenol in piglets[J].J Vet Sci,2010,11(2):107-113.
[25]	吉艺宽.饲料中霉菌毒素对猪免疫系统的影响[J].广东畜牧兽医科技,2018,43(4):13-15.JI Y K.Impact of mycotoxin in feed on immune system in pigs[J].Guangdong Journal of Animal and Veterinary Science, 2018,43(4):13-15.(in Chinese)
[26]	SKIEPKO N,PRZYBYLSKA-GORNOWICZ B,GAJE,CKA M,et al.Effects of deoxynivalenol and zearalenone on the histology and ultrastructure of pig liver[J].Toxins (Basel),2020,12(7):463.
[27]	GEREZ J R,PINTON P,CALLU P,et al.Deoxynivalenol alone or in combination with nivalenol and zearalenone induce systemic histological changes in pigs[J].Exp Toxicol Pathol,2015,67(2):89-98.
[28]	TIEMANN U,DÄNICKE S.In vivo and in vitro effects of the mycotoxins zearalenone and deoxynivalenol on different non-reproductive and reproductive organs in female pigs:a review[J].Food Addit Contam,2007,24(3):306-314.
[29]	REN Z H,GUO C Y,HE H Y,et al.Effects of deoxynivalenol on mitochondrial dynamics and autophagy in pig spleen lymphocytes[J].Food Chem Toxicol,2020,140:111357.
[30]	PRZYBYLSKA-GORNOWICZ B,LEWCZUK B,PRUSIK M,et al.The effects of deoxynivalenol and zearalenone on the pig large intestine.A light and electron microscopy study[J].Toxins (Basel),2018,10(4):148.
[31]	BRACARENSE A P F L,LUCIOLI J,GRENIER B,et al.Chronic ingestion of deoxynivalenol and fumonisin,alone or in interaction,induces morphological and immunological changes in the intestine of piglets[J].Br J Nutr,2012,107(12):1776-1786.
[32]	PINTON P,TSYBULSKYY D,LUCIOLI J,et al.Toxicity of deoxynivalenol and its acetylated derivatives on the intestine:differential effects on morphology,barrier function,tight junction proteins,and mitogen-activated protein kinases[J]. Toxicol Sci,2012,130(1):180-190.
[33]	AWAD W A,RAZZAZI-FAZELI E,BÖHM J,et al.Influence of deoxynivalenol on the D-glucose transport across the isolated epithelium of different intestinal segments of laying hens[J].J Anim Physiol Anim Nutr (Berl),2007,91(5-6):175-180.
[34]	MARESCA M,MAHFOUD R,GARMY N,et al.The mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells[J].J Nutr,2002,132(9):2723-2731.
[35]	GHAREEB K,AWAD W A,BÖHM J,et al.Impacts of the feed contaminant deoxynivalenol on the intestine of monogastric animals:poultry and swine[J].J Appl Toxicol,2015,35(4):327-337.
[36]	孙文涛,高文博,戴美玲,等.镰刀菌毒素对断奶仔猪子宫组织结构、Hsp70分布和表达的影响[J].畜牧兽医学报, 2017,48(6):1035-1043.SUN W T,GAO W B,DAI M L,et al.Effect of dietary Fusarium toxin on histological structure,distribution and expression of Hsp70 in the uterus of post-weaning piglets[J].Acta Veterinaria et Zootechnica Sinica,2017,48(6):1035-1043.(in Chinese)
[37]	陈亚,魏全伟,杜文超,等.乳果糖和富氢水对断奶仔猪采食霉变玉米后引起卵巢机能障碍的缓解作用[J].畜牧兽医学报, 2018, 49(12):2641-2651.CHEN Y,WEI Q W,DU W C,et al.Mitigation of lactulose and hydrogen-rich water on ovarian dysfunction caused by dietary contaminated corn in weaned piglets[J].Acta Veterinaria et Zootechnica Sinica,2018,49(12):2641-2651.(in Chinese)
[38]	YANG M,WU X D,ZHANG W,et al.Transcriptional analysis of deoxynivalenol-induced apoptosis of sow ovarian granulosa cell[J].Reprod Domest Anim,2020,55(2):217-228.
[39]	CAO L,ZHAO J,XU J R,et al.N-acetylcysteine ameliorate cytotoxic injury in piglets sertoli cells induced by zearalenone and deoxynivalenol[J].Environ Sci Pollut Res Int,2021,28(42):60276-60289.
[40]	PESTKA J J.Deoxynivalenol-induced proinflammatory gene expression:mechanisms and pathological sequelae[J].Toxins (Basel),2010,2(6):1300-1317.
[41]	ZHANG H,DENG X W,ZHOU C,et al.Deoxynivalenol induces inflammation in IPEC-J2 cells by activating P38 mapk and Erk1/2[J].Toxins (Basel),2020,12(3):180.
[42]	PESTKA J J,ZHOU H R,MOON Y,et al.Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes:unraveling a paradox[J].Toxicol Lett,2004,153(1):61-73.
[43]	ZHOU H R,ISLAM Z,PESTKA J J.Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol[J].Toxicol Sci,2005,87(1):113-122.
[44]	SOBROVA P,ADAM V,VASATKOVA A,et al.Deoxynivalenol and its toxicity[J].Interdiscip Toxicol,2010,3(3):94-99.
[45]	PESTKA J J,YAN D,KING L E.Flow cytometric analysis of the effects of in vitro exposure to vomitoxin (deoxynivalenol) on apoptosis in murine T,B and IgA+ cells[J].Food Chem Toxicol,1994,32(12):1125-1136.
[46]	PINTON P,ACCENSI F,BEAUCHAMP E,et al.Ingestion of deoxynivalenol (DON) contaminated feed alters the pig vaccinal immune responses[J].Toxicol Lett,2008,177(3):215-222.
[47]	LESSARD M,SAVARD C,DESCHENE K,et al.Impact of deoxynivalenol (DON) contaminated feed on intestinal integrity and immune response in swine[J].Food Chem Toxicol,2015,80:7-16.
[48]	VATZIA E,PIERRON A,SAALMVLLER A,et al.Deoxynivalenol affects proliferation and expression of activation-related molecules in major porcine T-cell subsets[J].Toxins (Basel),2019,11(11):644.
[49]	GAUTHIER T,WACHÉ Y,LAFFITTE J,et al.Deoxynivalenol impairs the immune functions of neutrophils[J].Mol Nutr Food Res,2013,57(6):1026-1036.
[50]	SUNDSTØL ERIKSEN G,PETTERSSON H,LUNDH T.Comparative cytotoxicity of deoxynivalenol,nivalenol,their acetylated derivatives and de-epoxy metabolites[J].Food Chem Toxicol,2004,42(4):619-624.
[51]	TIEMANN U,VIERGUTZ T,JONAS L,et al.Influence of the mycotoxins α-and β-zearalenol and deoxynivalenol on the cell cycle of cultured porcine endometrial cells[J].Reprod Toxicol,2003,17(2):209-218.
[52]	萧晟,刘丹丹,甘芳,等.脱氧雪腐镰刀菌烯醇对IPEC-J2细胞增殖、凋亡和屏障功能的影响及其自噬机制[J].南京农业大学学报,2019,42(4):746-751.XIAO S,LIU D D,GAN F,et al.Effects of deoxynivalenol on the proliferation,apoptosis and barrier function of IPEC-J2 cells and its autophagy mechanisms[J].Journal of Nanjing Agricultural University,2019,42(4):746-751.(in Chinese)
[53]	SUN X M,ZHANG X H,WANG H Y,et al.Effects of sterigmatocystin,deoxynivalenol and aflatoxin G1 on apoptosis of human peripheral blood lymphocytes in vitro[J].Biomed Environ Sci,2002,15(2):145-152.
[54]	YANG C,SONG G,LIM W.Effects of mycotoxin-contaminated feed on farm animals[J].J Hazard Mater,2020,389:122087.
[55]	KANG R F,LI R N,DAI P Y,et al.Deoxynivalenol induced apoptosis and inflammation of IPEC-J2 cells by promoting ROS production[J].Environ Pollut,2019,251:689-698.
[56]	黎相广.呕吐毒素抑制猪肠上皮细胞增殖和干细胞扩增的机制研究[D].广州:华南农业大学,2017.LI X G.Mechanisms of deoxynivalenol-induced inhibition on pig intestinal epithelial cell proliferation and stem cell expansion[D].Guangzhou:South China Agricultural University,2017.(in Chinese)
[57]	WANG X C,ZHANG Y F,ZHAO J,et al.Deoxynivalenol induces inflammatory injury in IPEC-J2 cells via NF-κB signaling pathway[J].Toxins (Basel),2019,11(12):733.
[58]	YU Y H,LAI Y H,HSIAO F S H,et al.Effects of deoxynivalenol and mycotoxin adsorbent agents on mitogen-activated protein kinase signaling pathways and inflammation-associated gene expression in porcine intestinal epithelial cells[J].Toxins (Basel),2021,13(5):301.
[59]	BECKER C,REITER M,PFAFFL M W,et al.Expression of immune relevant genes in pigs under the influence of low doses of deoxynivalenol (DON)[J].Mycotoxin Res,2011,27(4):287-293.
[60]	陈祥兴,张崇玉,黄丽波,等.镰刀菌毒素对断奶仔猪肠道IL-1β和IL-6分布和表达的影响[J].畜牧兽医学报,2016, 47(10):2126-2135.CHEN X X,ZHANG C Y,HUANG L B,et al.Effects of Fusarium toxins on IL-1β and IL-6 in post-weaning piglets[J].Acta Veterinaria et Zootechnica Sinica,2016,47(10):2126-2135.(in Chinese)
[61]	LI X G,ZHU M,CHEN M X,et al.Acute exposure to deoxynivalenol inhibits porcine enteroid activity via suppression of the Wnt/β-catenin pathway[J].Toxicol Lett,2019,305:19-31.
[62]	JIANG Q,YIN J,CHEN J S,et al.4-Phenylbutyric acid accelerates rehabilitation of barrier function in IPEC-J2 cell monolayer model[J].Anim Nutr,2021,7(4):1061-1069.
[63]	PIERRON A,ALASSANE-KPEMBI I,OSWALD I P.Impact of two mycotoxins deoxynivalenol and fumonisin on pig intestinal health[J].Porcine Health Manag,2016,2:21.
[64]	ESCRIV L,FONT G,MANYES L.In vivo toxicity studies of Fusarium mycotoxins in the last decade:a review[J].Food Chem Toxicol,2015,78:185-206.
[65]	XU Y F,CHEN X L,YU L C,et al.SLC4A11 and MFSD3 gene expression changes in deoxynivalenol treated IPEC-J2 cells[J].Front Genet,2021,12:697883.
[66]	赵呈祥.呕吐毒素诱导猪小肠上皮细胞转录组和全基因组DNA甲基化分析[D].扬州:扬州大学,2019.ZHAO C X.Transcriptome and genome-wide DNA methylome analysis of porcine intestinal epithelial cells upon deoxynivalenol exposure[D].Yangzhou:Yangzhou University,2019.(in Chinese)
[67]	SEGURA-WANG M,GRENIER B,ILIC S,et al.MicroRNA expression profiling in porcine liver,jejunum and serum upon dietary DON exposure reveals candidate toxicity biomarkers[J].Int J Mol Sci,2021,22(21):12043.
[68]	WANG H F,ZHOU Y J,XU C,et al.Genome-wide transcriptional profiling and functional analysis reveal miR-330-MAPK15 axis involving in cellular responses to deoxynivalenol exposure[J].Chemosphere,2022,298:134199.
[69]	XIE M Y,CHEN T,XI Q Y,et al.Porcine milk exosome miRNAs protect intestinal epithelial cells against deoxynivalenol-induced damage[J].Biochem Pharmacol,2020,175:113898.
[70]	WU L,WANG W C,YAO K,et al.Effects of dietary arginine and glutamine on alleviating the impairment induced by deoxynivalenol stress and immune relevant cytokines in growing pigs[J].PLoS One,2013,8(7):e69502.
[71]	DUAN J L,YIN J,WU M M,et al.Dietary glutamate supplementation ameliorates mycotoxin-induced abnormalities in the intestinal structure and expression of amino acid transporters in young pigs[J].PLoS One,2014,9(11):e112357.
[72]	WU L,LIAO P,HE L Q,et al.Dietary L-arginine supplementation protects weanling pigs from deoxynivalenol-induced toxicity[J].Toxins (Basel),2015,7(4):1341-1354.
[73]	胡永婷,李彦明,李颖靓.酵母培养物降低黄曲霉毒素和呕吐毒素对猪生长性能、器官健康和免疫状态影响的研究[J].中国饲料,2019(10):45-49.HU Y T,LI Y M,LI Y L.The study of effects of yeast culture supplementation on aflatoxin anddeoxynivalenol contaminated feed on growth performance,organ health and immune status of pigs[J].China Feed,2019(10):45-49.(in Chinese)
[74]	ZHANG L,MA R,ZHU M X,et al.Effect of deoxynivalenol on the porcine acquired immune response and potential remediation by a novel modified HSCAS adsorbent[J].Food Chem Toxicol,2020,138:111187.
[75]	HORKY P,GRUBEROVA H A,AULICHOVA T,et al.Protective effect of a new generation of activated and purified bentonite in combination with yeast and phytogenic substances on mycotoxin challenge in pigs[J].PLoS One,2021,16(10):e0259132.
[76]	SANTOS E V,FONTES D O,DA SILVEIRA BENFATO M,et al.Mycotoxin deactivator improves performance,antioxidant status,and reduces oxidative stress in nursery pigs fed diets containing mycotoxins[J].J Anim Sci,2021,99(10):skab277.
[77]	GARCÍA G R,PAYROS D,PINTON P,et al.Intestinal toxicity of deoxynivalenol is limited by Lactobacillus rhamnosus RC007 in pig jejunum explants[J].Arch Toxicol,2018,92(2):983-993.
[78]	REDDY K E,KIM M,KIM K H,et al.Effect of commercially purified deoxynivalenol and zearalenone mycotoxins on microbial diversity of pig cecum contents[J].Anim Biosci,2021,34(2):243-255.
[79]	GRENIER B,BRACARENSE A P F L,SCHWARTZ H E,et al.Biotransformation approaches to alleviate the effects induced by Fusarium mycotoxins in swine[J].J Agric Food Chem,2013,61(27):6711-6719.
[80]	GARCIA G R,DOGI C A,POLONI V L,et al.Beneficial effects of Saccharomyces cerevisiae RC016 in weaned piglets:in vivo and ex vivo analysis[J].Benef Microbes,2019,10(1):33-42.
[81]	ALASSANE-KPEMBI I,PINTON P,HUPÉ J F,et al.Saccharomyces cerevisiae boulardii reduces the deoxynivalenol-induced alteration of the intestinal transcriptome[J].Toxins (Basel),2018,10(5):199.
[82]	TANG M,YUAN D X,LIAO P.Berberine improves intestinal barrier function and reduces inflammation, immunosuppression, and oxidative stress by regulating the NF-κB/MAPK signaling pathway in deoxynivalenol-challenged piglets[J].Environ Pollut, 2021,289:117865.
[83]	QIU Y Q,YANG J,WANG L,et al.Dietary resveratrol attenuation of intestinal inflammation and oxidative damage is linked to the alteration of gut microbiota and butyrate in piglets challenged with deoxynivalenol[J].J Anim Sci Biotechnol,2021,12(1):71.
[84]	XU X X,YAN G R,CHANG J,et al.Astilbin ameliorates deoxynivalenol-induced oxidative stress and apoptosis in intestinal porcine epithelial cells (IPEC-J2)[J].J Appl Toxicol,2020,40(10):1362-1372.
[85]	XU X X,CHANG J,WANG P,et al.Effect of chlorogenic acid on alleviating inflammation and apoptosis of IPEC-J2 cells induced by deoxyniyalenol[J].Ecotoxicol Environ Saf,2020,205:111376.
[86]	RAJPUT S A,LIANG S J,WANG X Q,et al.Lycopene protects intestinal epithelium from deoxynivalenol-induced oxidative damage via regulating Keap1/Nrf2 signaling[J].Antioxidants (Basel),2021,10(9):1493.