The Molecular Mechanisms of Protective Role of Se on the G0/G1 Phase Arrest Caused by AFB1 in Broiler’s Thymocytes
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This research was designed to explore the protective effects of sodium selenite on G0/G1 phase arrest induced by AFB1 in thymocytes of broilers. Two hundred eighty-eight Cobb broilers were divided into control group, + Se group (0.4 mg/kg Se), AFB1 group (0.6 mg/kg AFB1), and AFB1 + Se group (0.6 mg/kg AFB1 + 0.4 mg/kg Se). The results revealed that 0.4 mg/kg Se supplement in diets could improve the AFB1-induced histological lesions in the thymus consisting of the more vacuoles and nuclear debris in thymic cortical area. The results of flow cytometric detect showed that 0.4 mg/kg Se relieved the G0/G1 phase arrest caused by AFB1 in thymocytes. The results of transcription levels of ATM, p53, p21, p27, p15, p16, CyclinD1, CyclinE, Cdk6, Cdk2, and PCNA genes by qRT-PC, and protein expression level of PCNA by immunohistochemistry demonstrated that 0.4 mg/kg Se could reduce the adverse effects of AFB1 on these parameters. In conclusion, Se could relieve AFB1-induced G0/G1 phase arrest by p15 (or p16)-CyclinD1/Cdk6, ATM-p53-p21-CyclinE/Cdk2, p27-CyclinE/Cdk2 pathways.
KeywordsSodium selenite AFB1 Cell cycle G0/G1 phase Thymus
This work was supported by the program for Changjiang Scholars and University Innovative Research Team (PCSIRT) (No. 0848) and the Education Department of Sichuan Province (2012FZ0066) and (2013FZ0072).
Compliance with Ethical Standards
The use of broilers and all experimental procedures involving animals were approved by the Animal Health and Care Committee of Sichuan Agricultural University (approval No. SYXK2014-187).
Conflict of Interest
The authors declare that they have no conflicts of interest.
- 4.Lakkawar AW, Chattopadhyay SK, Johri TS (2004) Experimental aflatoxin B1 toxicosis in young rabbits-a clinical and patho-anatomical study. Anatol Stud 36(12):467–472Google Scholar
- 7.Cancer IAFO (1993) Some naturally occurring substances: food items and constituents, heterocyclic aromatic amines and mycotoxins. CarcinógenosGoogle Scholar
- 12.Ezekiel CN, Alabi OA, Anokwuru CP, Oginni O (2011) Studies on dietary aflatoxin-induced genotoxicity using two in vivo bioassays. Arch Appl Sci Res 2:97–106Google Scholar
- 13.Jacotot E, Ferri KF, Kroemer G (2000) Apoptosis and cell cycle: distinct checkpoints with overlapping upstream control. Pathol Biol (Paris) 48(3):271Google Scholar
- 16.Yu ZQ, Wang FY, Liang N, Wang CH, Peng X, Fang J, Cui HM, Muhammad JM, Lai WM (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 168(1):242–251. https://doi.org/10.1007/s12011-015-0344-1 CrossRefGoogle Scholar
- 24.Zhang SQ, Peng X, Fang J, Cui HM, Zuo ZC, Chen ZL (2014) Effects of aflatoxin B1 exposure and sodium selenite supplementation on the histology, cell proliferation, and cell cycle of jejunum in broilers. Biol Trace Elem Res 160(1):32–40. https://doi.org/10.1007/s12011-014-0009-5 CrossRefGoogle Scholar
- 26.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. https://doi.org/10.1016/j.fct.2013.06.032 Google Scholar
- 28.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 4:1–12Google Scholar
- 29.Liu C, Zuo Z, Zhu P, Zheng Z, Xi P, Jing F, Cui H, Yi Z, Ping O, Yi G (2017) Sodium selenite prevents suppression of mucosal humoral response by AFB1 in broiler’s cecal tonsil. Oncotarget 8(33):54215–54226Google Scholar
- 31.Kaoud HA (2015) Innovative methods for the amelioration of aflatoxin (AFB1) effect in broiler chicks. Sjar Net 1(2):19–24Google Scholar
- 33.Shini S, Kaiser P (2009) Effects of stress, mimicked by administration of corticosterone in drinking water, on the expression of chicken cytokine and chemokine genes in lymphocytes. Stress-The International Journal on the Biology of Stress 12(5):388–399. https://doi.org/10.1080/10253890802526894 CrossRefGoogle Scholar
- 45.Smorodinsky NI, Shiloh Y (2000) Enhanced phosphorylation of p53 by ATM in response to DNA damageGoogle Scholar
- 47.Nakatsuka A, Wada J, Hida K, Hida A, Eguchi J, Teshigawara S, Murakami K, Kanzaki M, Inoue K, Terami T, katayama A, Ogawa D, Kagechika H, Makino H (2012) RXR antagonism induces G0/G1 cell cycle arrest and ameliorates obesity by up-regulating the p53-p21(Cip1) pathway in adipocytes. J Pathol 226(5):784–795. https://doi.org/10.1002/path.3001 CrossRefGoogle Scholar
- 48.Orlando S, Gallastegui E, Besson A, Abril G, Aligué R, Pujol MJ, Bachs O (2015) P27Kip1 and p21Cip1 collaborate in the regulation of transcription by recruiting cyclin-Cdk complexes on the promoters of target genes. Nucleic Acids Res 43(14):6860–6873. https://doi.org/10.1093/nar/gkv593 CrossRefGoogle Scholar
- 55.Gu X, Xu ZY, Zhu LY, Wang LF, Li K, Pei Q (2013) Dual control of Shuanghuang Shengbai granule on upstream and downstream signal modulators of CyclinD-CDK4/6 signaling pathway of cell cycle in Lewis-bearing mice with cyclophosphamide-induced myelosuppression. Oncotargets & Therapy 6:199–209. https://doi.org/10.2147/OTT.S37407 Google Scholar
- 58.Mei F, Tang J, Tang Y, Zhen Y, Sun H (2005) Effect of selenium on protein P16 expression in the testicle spermatogonium of rat with colon cancer induced by azoxymethane. Acta Anatomica Sinica 53(6):63018–63021(63014)Google Scholar
- 59.Su Y, Tang JM, Tang Y, Gao HY (2005) Effect of Na2SeO3 on experimental carcinogenesis of stomach and on p53 and p16 expression. Acta Anatomica Sinica 36(2):196–198Google Scholar