Abstract
Aflatoxin B1 (AFB1) is a naturally occurring secondary metabolites of Aspergillus flavus and Aspergillus parasiticus, and is the most toxic form of aflatoxins. Selenium (Se) with antioxidant and detoxification functions is one of the essential trace elements for human beings and animals. This study aims to evaluate the protective effects of Se on AFB1-induced tissue damage and cell cycle arrest in bursa of Fabricius (BF) of chickens. The results showed that a dietary supplement of 0.4 mg·kg−1 Se alleviated the histological lesions induced by AFB1, as demonstrated by decreasing vacuoles and nuclear debris, and relieving oxidative stress. Furthermore, flow cytometry studies showed that a Se supplement protected AFB1-induced G2M phase arrest at 7 days and G0G1 phase arrest at 14 and 21 days. Moreover, the mRNA expression results of ATM, Chk2, p53, p21, cdc25, PCNA, cyclin D1, cyclin E1, cyclin B3, CDK6, CDK2, and cdc2 indicated that Se supplement could restore these parameters to be close to those in the control group. It is concluded that a dietary supplement of 0.4 mg kg−1 Se could diminish AFB1-induced immune toxicity in chicken’s BF by alleviating oxidative damage and cell cycle arrest through an ATM-Chk2-cdc25 route and the ATM-Chk2-p21 pathway.
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References
Trucksess MW, Stack ME, Nesheim S, Albert RH, Romer TR (1994) Multifunctional column coupled with liquid chromatography for determination of aflatoxins B1, B2, G1, and G2 in corn, almonds, brazil nuts, peanuts, and pistachio nuts: collaborative study. J AOAC Int 77(6):1512–1521
Cancer IAFO (1993) Some naturally occurring substances: food items and constituents, heterocyclic aromatic amines and mycotoxins. Carcinógenos
Jr CR (1993) Biological action of mycotoxins. J Dairy Sci 76(3):880–891
Wang JS, Groopman JD (1999) DNA damage by mycotoxins. Mutat Res Fundam Mol Mech Mutagen 424(1–2):167–181
Lu X, Hu B, Shao L, Tian Y, Jin T, Jin Y, Ji S, Fan X (2013) Integrated analysis of transcriptomics and metabonomics profiles in aflatoxin B1-induced hepatotoxicity in rat. Food Chem Toxicol 55(3):444–455
Bailey EA, Iyer RS, Stone MP, Harris TM, Essigmann JM (1996) Mutational properties of the primary aflatoxin B1-DNA adduct. Proc Natl Acad Sci U S A 93(4):1535–1539
Meissonnier GM, Pinton P, Laffitte J, Cossalter AM, Gong YY, Wild CP, Bertin G, Galtier P, Oswald IP (2008) Immunotoxicity of aflatoxin B1: impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression. Toxicol Appl Pharmacol 231(2):142–149
Shuaib FMB, Ehiri J, Abdullahi A, Williams JH, Jolly PE (2010) Reproductive health effects of aflatoxins: a review of the literature. Reprod Toxicol 29(3):262–270
Rieswijk L, Claessen SM, Bekers O, Van HM, Theunissen DH, Jennen DG, de Kok TM, Kleinjans JC, van Breda SG (2016) Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology s 350–352:31–39
Cooper MD, Peterson RDA, Ann SM, Good RA (2006) The functions of the thymus system and the bursa system in the chicken. J Immunol 176(11):6370–6404
Giambrone JJ, Ewert DL, Wyatt RD, Eidson CS (1978) Effect of aflatoxin on the humoral and cell-mediated immune systems of the chicken. Am J Vet Res 39(2):305–308
Bakheet SA, Attia SM, Alwetaid MY, Ansari MA, Zoheir KMA, Nadeem A, Al-Shabanah OA, Al-Harbi MM, Ahmad SF (2016) β-1,3-Glucan reverses aflatoxin B1 -mediated suppression of immune responses in mice. Life Sci 152:1–13
Yin H, Jiang M, Peng X, Cui H, Zhou Y, He M, Zuo Z, Ouyang P, Fan J, Fang J (2016) The molecular mechanism of G2M cell cycle arrest induced by AFB1 in the jejunum. Oncotarget 7(24):35592–35606
Yang X, Zhang Z, Wang X, Wang Y, Zhang X, Lu H, Wang SL (2013) Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage. Toxicol Appl Pharmacol 270(2):114–121
Liu C, Yu H, Zhang Y, Li D, Xing X, Chen L, Zeng X, Xu D, Fan Q, Xiao Y (2015) Upregulation of miR-34a-5p antagonizes AFB1-induced genotoxicity in F344 rat liver. Toxicon Off J Int Soc Toxinol 106:46–56
Farombi EO, Adepoju BF, Ola-Davies OE, Emerole GO (2005) Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural bioflavonoid of Garcinia kola seeds. Eur J Cancer Prev 14(3):207–214
Mary VS, Theumer MG, Arias SL, Rubinstein HR (2012) Reactive oxygen species sources and biomolecular oxidative damage induced by aflatoxin B1 and fumonisin B1 in rat spleen mononuclear cells. Toxicology 302(2–3):299–307
Althnaian T (2016) Gene expression and activities of antioxidant enzymes in kidneys of rats intoxicated with aflatoxin B1. 16(3):65–71
Liu J, Song WJ, Zhang NY, Tan J, Krumm CS, Sun LH, Qi DS (2016) Biodetoxification of aflatoxin B1 in cottonseed meal by fermentation of Cellulosimicrobium funkei in duckling diet. Poult Sci 96(4):923–930
Abbès S, Ben S-AJ, Jebali R, Younes RB, Oueslati R (2015) Interaction of aflatoxin B1 and fumonisin B1 in mice causes immunotoxicity and oxidative stress: possible protective role using lactic acid bacteria. J Immunotoxicol 14:46–54
Rayman MP (2012) Selenium and human health. Lancet 379(9822):1256–1268
Ferguson LR, Karunasinghe N, Zhu S, Wang AH (2012) Selenium and its’ role in the maintenance of genomic stability. Mutat Res Fundam Mol Mech Mutagen 733(1–2):100–110
Zeng H (2009) Selenium as an essential micronutrient: roles in cell cycle and apoptosis. Molecules 14(3):1263–1278
Van CR, Robberecht H, Van VV, Deelstra H (2004) Comparison of the serum selenium content of healthy adults living in the Antwerp region (Belgium) with recent literature data. J Trace Elem Med Biol 18(1):99–112
Parveen F, Nizamani ZA, Gan F, Chen X, Shi X, Kumbhar S, Zeb A, Huang K (2014) Protective effect of selenomethionine on aflatoxin B1-induced oxidative stress in MDCK cells. Biol Trace Elem Res 157(3):266–274
Fang J, Yin H, Zheng Z, Zhu P, Peng X, Zuo Z, Cui H, Zhou Y, Ouyang P, Geng Y (2017) The molecular mechanisms of protective role of Se on the G2/M phase arrest of jejunum caused by AFB1. Biol Trace Elem Res (4): 1–12
Yu Z, Wang F, Liang N, Wang C, Peng X, Fang J, Cui H, Mughal MJ, Lai W (2015) Effect of selenium supplementation on apoptosis and cell cycle blockage of renal cells in broilers fed a diet containing aflatoxin B1. Biol Trace Elem Res 5(1):242–251
Shu H, Hu JF, Song S, Da H, Xu H, Gang Q, Huang K (2016) Selenium alleviates aflatoxin B1-induced immune toxicity through improving glutathione peroxidase 1 and selenoprotein S expression in primary porcine splenocytes. J Agric Food Chem 64(6):1385–1393
Venkateswaran V, Klotz LH, Fleshner NE (2002) Selenium modulation of cell proliferation and cell cycle biomarkers in human prostate carcinoma cell lines. Cancer Res 62(9):2540–2545
Zhong W, Oberley TD (2001) Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line. Cancer Res 61(19):7071–7078
El-Bayoumy K (2001) The protective role of selenium on genetic damage and on cancer. Mutat Res 475(1):123–139
Potworowski EF (1972) T and B lymphocytes. Organ and age distribution in the chicken. Immunology 23(2):199–204
Peng X, Bai S, Ding X, Zhang K (2017) Pathological impairment, cell cycle arrest and apoptosis of thymus and bursa of Fabricius induced by aflatoxin-contaminated corn in broilers. Int J Environ Res Public Health 14(1):77–88
Chen K, Jing F, Xi P, Cui H, Jin C, Wang F, Chen Z, Zuo Z, Deng J, Lai W (2014) Effect of selenium supplementation on aflatoxin B1 -induced histopathological lesions and apoptosis in bursa of Fabricius in broilers. Food Chem Toxicol 74(74):91–97
Dale N (1994) National research council nutrient requirements of poultry-ninth revised edition (1994). J Appl Poult Res 3(1):101–101
Chen J, Chen K, Yuan S, Peng X, Fang J, Wang F, Cui H, Chen Z, Yuan J, Geng Y (2016) Effects of aflatoxin B1 on oxidative stress markers and apoptosis of spleens in broilers. Toxicol Ind Health 32(2):278–284
Rawal S, Kim JE, Jr CR (2010) Aflatoxin B1 in poultry: toxicology, metabolism and prevention. Res Vet Sci 89(3):325–331
Peng X, Chen K, Chen J, Fang J, Cui H, Zuo Z, Deng J, Chen Z, Geng Y, Lai W (2016) Aflatoxin B1 affects apoptosis and expression of Bax, Bcl-2, and Caspase-3 in thymus and bursa of fabricius in broiler chickens. Environ Toxicol 31(9):1113–1120
Chen T, Cui H, Cui Y, Bai C, Gong T, Peng X (2011) Cell-cycle blockage associated with increased apoptotic cells in the thymus of chickens fed on diets high in fluorine. Hum Exp Toxicol 30(7):685–692
Mughal MJ, Xi P, Yi Z, Jing F (2017) Aflatoxin B1 invokes apoptosis via death receptor pathway in hepatocytes. Oncotarget 8(5):8239–8249
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25(4):402–408
Girish C, Smith T (2008) Impact of feed-borne mycotoxins on avian cell-mediated and humoral immune responses. World Mycotoxin J 1(2):105–121
Raju MV, Devegowda G (2000) Influence of esterified-glucomannan on performance and organ morphology, serum biochemistry and haematology in broilers exposed to individual and combined mycotoxicosis (aflatoxin, ochratoxin and T-2 toxin). Br Poult Sci 41(5):640–650
Shamberger RJ, Frost DV (1969) Possible protective effect of selenium against human cancer. Can Med Assoc J 100(14):682
Hatfield DL (2006) Selenium: its molecular biology and role in human health, 2th edn. Springer, USA
Wang F, Shu G, Peng X, Fang J, Chen K, Cui H, Chen Z, Zuo Z, Deng J, Geng Y (2013) Protective effects of sodium selenite against aflatoxin B1-induced oxidative stress and apoptosis in broiler spleen. Int J Environ Res Public Health 10(7):2834–2844
Chen K, Shu G, Peng X, Fang J, Cui H, Chen J, Wang F, Chen Z, Zuo Z, Deng J (2013) Protective role of sodium selenite on histopathological lesions, decreased T-cell subsets and increased apoptosis of thymus in broilers intoxicated with aflatoxin B1. Food Chem Toxicol 59(3):446–454
Wang SL (2006) Efficient activation of aflatoxin B1 by cytochrome P450 2A13, an enzyme predominantly expressed in human respiratory tract. Int J Cancer 118(11):2665–2671
OmuraT SR (1964) The carbon monoxide-binding pigment of liver microsomes I. Evidence for its hemoprotein nature. J Biol Chem 239(7):2370–2378
Ortiz dM, Paul R (2015) Cytochrome P450: structure, mechanism, and biochemistry. In: Activation of molecular oxygen in cytochromes P450, 4th edn. Plenum Press, UAS, p 69
Devasagayam TP, Tilak JC, Boloor KK, Sane KS, Ghaskadbi SS, Lele RD (2004) Free radicals and antioxidants in human health: current status and future prospects. J Assoc Physicians India 52(794804):794–804
Mannuss A, Trapp O, Puchta H (2003) Gene regulation in response to DNA damage. Anatolian. J Cardiol 3(4):313–318
Matsuoka S, Rotman G, Ogawa A, Shiloh Y, Tamai K, Elledge SJ (2000) Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc Natl Acad Sci U S A 97(19):10389–10394
Nigg EA (2001) Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol 2(1):21–32
Zeng H (2002) Selenite and selenomethionine promote HL-60 cell cycle progression. J Nutr 132(4):674–679
Valesky EM, Hrgovic I, Doll M, Wang XF, Pinter A, Kleemann J, Kaufmann R, Kippenberger S, Meissner M (2015) Dimethylfumarate effectively inhibits lymphangiogenesis via p21 induction and G1 cell cycle arrest. Exp Dermatol 25(3):200–205
Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B (1998) Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282(5393):1497–1501
Kotoku N, Higashimoto K, Kurioka M, Arai M, Fukuda A, Sumii Y, Sowa Y, Sakai T, Kobayashi M (2014) Xylarianaphthol-1, a novel dinaphthofuran derivative, activates p21 promoter in a p53-independent manner. Bioorg Med Chem Lett 24(15):3389–3391
Buscemi G, Perego P, Carenini N, Nakanishi M, Chessa L, Chen J, Khanna KK, Delia D (2004) Activation of ATM and Chk2 kinases in relation to the amount of DNA strand breaks. Oncogene 23(46):7691–7700
Huang CY, Chang CW, Chen CR, Chuang CY, Chiang CS, Shu WY, Fan TC, Hsu IC (2014) Extremely low-frequency electromagnetic fields cause G1 phase arrest through the activation of the ATM-Chk2-p21 pathway. PLoS One 9(8):e104732–e104739
Haracska L, Torresramos CA, Johnson RE, Prakash S, Prakash L (2004) Opposing effects of ubiquitin conjugation and SUMO modification of PCNA on replicational bypass of DNA lesions in saccharomyces cerevisiae. Mol Cell Biol 24(10):4267–4274
Kannouche PL, Lehmann AR (2004) Ubiquitination of PCNA and the polymerase switch in human cells. Cell Cycle 3(8):1009–1011
Wang SC, Nakajima Y, Yu YL, Xia W, Chen CT, Yang CC, Mcintush EW, Li LY, Hawke DH, Kobayashi R (2006) Tyrosine phosphorylation controls PCNA function through protein stability. Nat Cell Biol 8(12):1359–1368
Funding
This work was funded by the program for the Changjiang Scholars and University Innovative Research Team (IRT 0848) and the Science and Technology Department of Sichuan Province (2012FZ0066 and 2013FZ0072) as well as the Huimin Project of Chengdu Science and Technology (2016-HM01-00337-SF).
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All procedures performed in studies involving animals were in accordance with the international guidelines and the laws and ethical standards of the Sichuan Agricultural University Animal Care and Use Committee (Approval No. 2012-024) where the studies were conducted.
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Hu, P., Zuo, Z., Wang, F. et al. The Protective Role of Selenium in AFB1-Induced Tissue Damage and Cell Cycle Arrest in Chicken’s Bursa of Fabricius. Biol Trace Elem Res 185, 486–496 (2018). https://doi.org/10.1007/s12011-018-1273-6
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DOI: https://doi.org/10.1007/s12011-018-1273-6