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Agaricus blazei Murill Polysaccharides Protect Against Cadmium-Induced Oxidative Stress and Inflammatory Damage in Chicken Spleens

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Abstract

Agaricus blazei Murill polysaccharide (ABP) has exhibited antioxidant and immunoregulatory activity. The aim of this study was to investigate the effect of ABP on cadmium (Cd)-induced antioxidant functions and inflammatory damage in chicken spleens. In this study, groups of 7-day-old chickens were fed with normal saline (0.2 mL single/day), CdCl2 (140 mg/kg/day), ABP (30 mg/mL, 0.2 mL single/day), and Cd + ABP (140 mg/kg/day + 0.2 mL ABP). Spleens were separated on the 20th, 40th, and 60th day for each group. The Cd contents, expression of melanoma-associated differentiation gene 5 (MDA5) and its downstream signaling molecules (interferon promoter-stimulating factor 1 (IPS-1), transcription factors interferon regulatory factor 3 (IRF3), and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB)), the content of cytokines (interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and beta interferon (IFN-β)), protein levels of heat shock proteins (HSPs), levels of malondialdehyde (MDA), activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and histopathological changes of spleens were detected on the 20th, 40th, and 60th day. The results showed that ABP significantly reduced the accumulation of Cd in the chicken spleens and reduced the expression of MDA5, IPS-1, IRF-3, and NF-κB; their downstream inflammatory cytokines, IL-1β, IL-6, TNF-α, and IFN-β; and the protein levels of HSPs (HSP60, HSP70, and HSP90) in spleens. The activities of antioxidant enzymes (SOD and GSH-Px) significantly increased, and the level of MDA decreased in the ABP + Cd group. The results indicate that ABP has a protective effect on Cd-induced damage in chicken spleens.

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References

  1. Van Maele-Fabry G, Lombaert N, Lison D (2016) Dietary exposure to cadmium and risk of breast cancer in postmenopausal women: a systematic review and meta-analysis. Environ Int 86:1–13

    Article  PubMed  CAS  Google Scholar 

  2. Sun H, Wang D, Zhou Z, Ding Z, Chen X, Xu Y, Huang L, Tang D (2016) Association of cadmium in urine and blood with age in a general population with low environmental exposure. Chemosphere 156:392–397

    Article  PubMed  CAS  Google Scholar 

  3. Gu X, Chen R, Hu G, Zhuang Y, Luo J, Zhang C, Guo X, Huang A, Cao H (2015) Cell apoptosis of caprine spleen induced by toxicity of cadmium with different levels of molybdenum. Environ Toxicol Pharmacol 40(1):49–56

    Article  PubMed  CAS  Google Scholar 

  4. Pollock B, Machin KL (2009) Corticosterone in relation to tissue cadmium, mercury and selenium concentrations and social status of male lesser scaup (Aythya affinis). Ecotoxicology 18(1):5–14

    Article  PubMed  CAS  Google Scholar 

  5. Liu S, FP X, Yang ZJ, Li M, Min YH, Li S (2014) Cadmium-induced injury and the ameliorative effects of selenium on chicken splenic lymphocytes: mechanisms of oxidative stress and apoptosis. Biol Trace Elem Res 160(3):340–351

    Article  PubMed  CAS  Google Scholar 

  6. Banos-Lara Mdel R, Ghosh A, Guerrero-Plata A (2013) Critical role of MDA5 in the interferon response induced by human metapneumovirus infection in dendritic cells and in vivo. J Virol 87(2):1242–1251

    Article  PubMed  CAS  Google Scholar 

  7. Poeck H, Ruland J (2012) From virus to inflammation: mechanisms of RIG-I-induced IL-1beta production. Eur J Cell Biol 91(1):59–64

    Article  PubMed  CAS  Google Scholar 

  8. Rietdijk ST, Burwell T, Bertin J, Coyle AJ (2008) Sensing intracellular pathogens—NOD-like receptors. Curr Opin Pharmacol 8(3):261–266

    Article  PubMed  CAS  Google Scholar 

  9. Dostert C, Meylan E, Tschopp J (2008) Intracellular pattern-recognition receptors. Adv Drug Deliv Rev 60(7):830–840

    Article  PubMed  CAS  Google Scholar 

  10. Quicke KM, Diamond MS, Suthar MS (2017) Negative regulators of the RIG-I-like receptor signaling pathway. Eur J Immunol 47(4):615–628

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Han J, Sun Y, Song W, Xu T (2017) microRNA-145 regulates the RLR signaling pathway in miiuy croaker after poly(I:C) stimulation via targeting MDA5. Dev Comp Immunol 68:79–86

    Article  PubMed  CAS  Google Scholar 

  12. Hartwig A (2010) Mechanisms in cadmium-induced carcinogenicity: recent insights. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 23(5):951–960

    Article  CAS  Google Scholar 

  13. Emmanouil C, Sheehan TM, Chipman JK (2007) Macromolecule oxidation and DNA repair in mussel (Mytilus edulis L.) gill following exposure to Cd and Cr(VI). Aquat Toxicol 82(1):27–35

    Article  PubMed  CAS  Google Scholar 

  14. Hu X, Zhang R, Xie Y, Wang H, Ge M (2017) The protective effects of polysaccharides from Agaricus blazei Murill against cadmium-induced oxidant stress and inflammatory damage in chicken livers. Biol Trace Elem Res 178(1):117–126

    Article  PubMed  CAS  Google Scholar 

  15. Fanhani JC, Murakami AE, Guerra AFQG, GRd N, Pedroso RB, Alves MCF (2016) Effect of Agaricus blazei in the diet of broiler chickens on immunity, serum parameters and antioxidant activity. Semina: Ciências Agrárias 37(4):2235

    Google Scholar 

  16. Mizuno T (1995) Bioactive biomolecules of mushrooms: food function and medicinal effect of mushroom fungi. Food Reviews International 11(1):5–21

    Article  Google Scholar 

  17. Cui L, Sun Y, Xu H, Xu H, Cong H, Liu J (2013) A polysaccharide isolated from Agaricus blazei Murill (ABP-AW1) as a potential Th1 immunity-stimulating adjuvant. Oncol Lett 6(4):1039–1044

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Liu Y, Zhang L, Zhu X, Wang Y, Liu W, Gong W (2015) Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type, which mediates inhibition of tumour immune-evasion via the Toll-like receptor 2 pathway. Immunology 146(3):379–391

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Gonzaga ML, Bezerra DP, Alves AP, de Alencar NM, Mesquita Rde O, Lima MW, Soares Sde A, Pessoa C, de Moraes MO, Costa-Lotufo LV (2009) In vivo growth-inhibition of Sarcoma 180 by an alpha-(1-->4)-glucan-beta-(1-->6)-glucan-protein complex polysaccharide obtained from Agaricus blazei Murill. J Nat Med 63(1):32–40

    Article  PubMed  CAS  Google Scholar 

  20. Sui Z, Yang R, Liu B, Gu T, Zhao Z, Shi D, Chang D (2010) Chemical analysis of Agaricus blazei polysaccharides and effect of the polysaccharides on IL-1beta mRNA expression in skin of burn wound-treated rats. Int J Biol Macromol 47(2):155–157

    Article  PubMed  CAS  Google Scholar 

  21. Wu S, Li F, Jia S, Ren H, Gong G, Wang Y, Lv Z, Liu Y (2014) Drying effects on the antioxidant properties of polysaccharides obtained from Agaricus blazei Murrill. Carbohydr Polym 103:414–417

    Article  PubMed  CAS  Google Scholar 

  22. Lv A, Ge M, Hu X, Liu W, Li G, Zhang R (2017) Effects of Agaricus blazei Murill polysaccharide on cadmium poisoning on the MDA5 signaling pathway and antioxidant function of chicken peripheral blood lymphocytes. Biological trace element research

    Google Scholar 

  23. Guo Y, Zhao P, Guo G, Hu Z, Tian L, Zhang K, Sun Y, Zhang X, Zhang W, Xing M (2016) Effects of arsenic trioxide exposure on heat shock protein response in the immune organs of chickens. Biol Trace Elem Res 169(1):134–141

    Article  PubMed  CAS  Google Scholar 

  24. Gill LW, Ring P, Casey B, Higgins NMP, Johnston PM (2017) Long term heavy metal removal by a constructed wetland treating rainfall runoff from a motorway. Sci Total Environ 601-602:32–44

    Article  PubMed  CAS  Google Scholar 

  25. Jin X, Xu Z, Zhao X, Chen M, Xu S (2017) The antagonistic effect of selenium on lead-induced apoptosis via mitochondrial dynamics pathway in the chicken kidney. Chemosphere 180:259–266

    Article  PubMed  CAS  Google Scholar 

  26. Li X, Xing M, Chen M, Zhao J, Fan R, Zhao X, Cao C, Yang J, Zhang Z, Xu S (2017) Effects of selenium-lead interaction on the gene expression of inflammatory factors and selenoproteins in chicken neutrophils. Ecotoxicol Environ Saf 139:447–453

    Article  PubMed  CAS  Google Scholar 

  27. Liu Q, Ji X, Ge Z, Diao H, Chang X, Wang L, Wu Q (2017) Role of connexin 43 in cadmium-induced proliferation of human prostate epithelial cells. Journal of applied toxicology : JAT 37(8):933–942

    Article  PubMed  CAS  Google Scholar 

  28. Manquian-Cerda K, Escudey M, Zuniga G, Arancibia-Miranda N, Molina M, Cruces E (2016) Effect of cadmium on phenolic compounds, antioxidant enzyme activity and oxidative stress in blueberry (Vaccinium corymbosum L.) plantlets grown in vitro. Ecotoxicol Environ Saf 133:316–326

    Article  PubMed  CAS  Google Scholar 

  29. Liu W, Zhao H, Wang Y, Jiang C, Xia P, Gu J, Liu X, Bian J, Yuan Y, Liu Z (2014) Calcium-calmodulin signaling elicits mitochondrial dysfunction and the release of cytochrome c during cadmium-induced apoptosis in primary osteoblasts. Toxicol Lett 224(1):1–6

    Article  PubMed  CAS  Google Scholar 

  30. Zou H, Zhuo L, Han T, Hu D, Yang X, Wang Y, Yuan Y, Gu J, Bian J, Liu X, Liu Z (2015) Autophagy and gap junctional intercellular communication inhibition are involved in cadmium-induced apoptosis in rat liver cells. Biochem Biophys Res Commun 459(4):713–719

    Article  PubMed  CAS  Google Scholar 

  31. Al-Dbass AM, Al-Daihan SK, Bhat RS (2012) Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats. Saudi journal of biological sciences 19(3):303–309

    Article  PubMed  PubMed Central  Google Scholar 

  32. de Jesus Pereira NC, Regis WC, Costa LE, de Oliveira JS, da Silva AG, Martins VT, Duarte MC, de Souza JR, Lage PS, Schneider MS, Melo MN, Soto M, Soares SA, Tavares CA, Chavez-Fumagalli MA, Coelho EA (2015) Evaluation of adjuvant activity of fractions derived from Agaricus blazei, when in association with the recombinant LiHyp1 protein, to protect against visceral leishmaniasis. Exp Parasitol 153:180–190

    Article  PubMed  CAS  Google Scholar 

  33. Bernardshaw S, Hetland G, Ellertsen LK, Tryggestad AM, Johnson E (2005) An extract of the medicinal mushroom Agaricus blazei Murill differentially stimulates production of pro-inflammatory cytokines in human monocytes and human vein endothelial cells in vitro. Inflammation 29(4–6):147–153

    PubMed  Google Scholar 

  34. Liu W, Ge M, Hu X, Lv A, Ma D, Huang X, Zhang R (2017) The effects of Agaricus blazei Murill polysaccharides on cadmium-induced apoptosis and the TLR4 signaling pathway of peripheral blood lymphocytes in chicken. Biological trace element research

  35. Pathak N, Khandelwal S (2006) Influence of cadmium on murine thymocytes: potentiation of apoptosis and oxidative stress. Toxicol Lett 165(2):121–132

    Article  PubMed  CAS  Google Scholar 

  36. Alvarez-Olmedo DG, Biaggio VS, Koumbadinga GA, Gomez NN, Shi C, Ciocca DR, Batulan Z, Fanelli MA, O'Brien ER (2017) Recombinant heat shock protein 27 (HSP27/HSPB1) protects against cadmium-induced oxidative stress and toxicity in human cervical cancer cells. Cell Stress Chaperones 22(3):357–369

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Nazir A, Saxena DK, Kar Chowdhuri D (2003) Induction of hsp70 in transgenic Drosophila: biomarker of exposure against phthalimide group of chemicals. Biochim Biophys Acta Gen Subj 1621(2):218–225

    Article  CAS  Google Scholar 

  38. Wang Z, Wu Z, Jian J, Lu Y (2009) Cloning and expression of heat shock protein 70 gene in the haemocytes of pearl oyster (Pinctada fucata, Gould 1850) responding to bacterial challenge. Fish & shellfish immunology 26(4):639–645

    Article  CAS  Google Scholar 

  39. Zhao P, Guo Y, Zhang W, Chai H, Xing H, Xing M (2017) Neurotoxicity induced by arsenic in Gallus Gallus: regulation of oxidative stress and heat shock protein response. Chemosphere 166:238–245

    Article  PubMed  CAS  Google Scholar 

  40. Truettner JS, Hu K, Liu CL, Dietrich WD, Hu B (2009) Subcellular stress response and induction of molecular chaperones and folding proteins after transient global ischemia in rats. Brain Res 1249:9–18

    Article  PubMed  CAS  Google Scholar 

  41. Gao Q, Song L, Ni D, Wu L, Zhang H, Chang Y (2007) cDNA cloning and mRNA expression of heat shock protein 90 gene in the haemocytes of Zhikong scallop Chlamys farreri. Comparative biochemistry and physiology Part B, Biochemistry & molecular biology 147(4):704–715

    Article  CAS  Google Scholar 

  42. Nemmiche S, Chabane-Sari D, Kadri M, Guiraud P (2012) Cadmium-induced apoptosis in the BJAB human B cell line: involvement of PKC/ERK1/2/JNK signaling pathways in HO-1 expression. Toxicology 300(3):103–111

    Article  PubMed  CAS  Google Scholar 

  43. Nemmiche S, Guiraud P (2016) Cadmium-induced oxidative damages in the human BJAB cells correlate with changes in intracellular trace elements levels and zinc transporters expression. Toxicology in vitro : an international journal published in association with BIBRA 37:169–177

    Article  CAS  Google Scholar 

  44. Oliveira RJ, Matuo R, da Silva AF, Matiazi HJ, Mantovani MS, Ribeiro LR (2007) Protective effect of beta-glucan extracted from Saccharomyces cerevisiae, against DNA damage and cytotoxicity in wild-type (k1) and repair-deficient (xrs5) CHO cells. Toxicology in vitro : an international journal published in association with BIBRA 21(1):41–52

    Article  CAS  Google Scholar 

  45. Oliveira RJ, Ribeiro LR, da Silva AF, Matuo R, Mantovani MS (2006) Evaluation of antimutagenic activity and mechanisms of action of beta-glucan from barley, in CHO-k1 and HTC cell lines using the micronucleus test. Toxicology in vitro : an international journal published in association with BIBRA 20(7):1225–1233

    Article  CAS  Google Scholar 

  46. Tohamy AA, El-Ghor AA, El-Nahas SM, Noshy MM (2003) β-Glucan inhibits the genotoxicity of cyclophosphamide, adriamycin and cisplatin. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 541(1–2):45–53

    Article  CAS  Google Scholar 

  47. Sahin E, Gumuslu S (2004) Cold-stress-induced modulation of antioxidant defence: role of stressed conditions in tissue injury followed by protein oxidation and lipid peroxidation. Int J Biometeorol 48(4):165–171

    Article  PubMed  CAS  Google Scholar 

  48. Dwivedi VK, Bhatanagar A, Chaudhary M (2012) Protective role of ceftriaxone plus sulbactam with VRP1034 on oxidative stress, hematological and enzymatic parameters in cadmium toxicity induced rat model. Interdiscip Toxicol 5(4):192–200

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Falfushinska HI, Romanchuk LD, Stolyar OB (2008) Different responses of biochemical markers in frogs (Rana ridibunda) from urban and rural wetlands to the effect of carbamate fungicide. Comparative biochemistry and physiology Toxicology & pharmacology : CBP 148(3):223–229

    Article  CAS  Google Scholar 

  50. Wang Y, Fang J, Leonard SS, Rao KM (2004) Cadmium inhibits the electron transfer chain and induces reactive oxygen species. Free Radic Biol Med 36(11):1434–1443

    Article  PubMed  CAS  Google Scholar 

  51. Li JL, Jiang CY, Li S, SW X (2013) Cadmium induced hepatotoxicity in chickens (Gallus domesticus) and ameliorative effect by selenium. Ecotoxicol Environ Saf 96:103–109

    Article  PubMed  CAS  Google Scholar 

  52. Kudr J, Nguyen HV, Gumulec J, Nejdl L, Blazkova I, Ruttkay-Nedecky B, Hynek D, Kynicky J, Adam V, Kizek R (2014) Simultaneous automatic electrochemical detection of zinc, cadmium, copper and lead ions in environmental samples using a thin-film mercury electrode and an artificial neural network. Sensors 15(1):592–610

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Lee JC, Son YO, Pratheeshkumar P, Shi X (2012) Oxidative stress and metal carcinogenesis. Free Radic Biol Med 53(4):742–757

    Article  PubMed  CAS  Google Scholar 

  54. Yuan SS, Lv ZM, Zhu AY, Zheng JL, CW W (2017) Negative effect of chronic cadmium exposure on growth, histology, ultrastructure, antioxidant and innate immune responses in the liver of zebrafish: preventive role of blue light emitting diodes. Ecotoxicol Environ Saf 139:18–26

    Article  PubMed  CAS  Google Scholar 

  55. Nemmiche S (2017) Oxidative signaling response to cadmium exposure. Toxicological sciences : an official journal of the Society of Toxicology 156(1):4–10

    CAS  Google Scholar 

  56. Black PH (2002) Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav Immun 16(6):622–653

    Article  PubMed  CAS  Google Scholar 

  57. Xu F, Liu S, Li S (2015) Effects of selenium and cadmium on changes in the gene expression of immune cytokines in chicken splenic lymphocytes. Biol Trace Elem Res 165(2):214–221

    Article  PubMed  CAS  Google Scholar 

  58. Li JL, Li S, Tang ZX, Xu SW (2010) Oxidative stress-mediated cytotoxicity of cadmium in chicken splenic lymphocytes. Toxicol Lett 196:S122

    Article  Google Scholar 

  59. Zheng JL, Yuan SS, CW W, Li WY (2016) Chronic waterborne zinc and cadmium exposures induced different responses towards oxidative stress in the liver of zebrafish. Aquat Toxicol 177:261–268

    Article  PubMed  CAS  Google Scholar 

  60. Zheng JL, Yuan SS, CW W, Lv ZM (2016) Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio). Aquat Toxicol 180:36–44

    Article  PubMed  CAS  Google Scholar 

  61. Ding Z, An K, Xie L, Wu W, Zhang R, Wang D, Fang Y, Chen H, Xiao S, Fang L (2017) Transmissible gastroenteritis virus infection induces NF-kappaB activation through RLR-mediated signaling. Virology 507:170–178

    Article  PubMed  CAS  Google Scholar 

  62. Lan W, Petznick A, Heryati S, Rifada M, Tong L (2012) Nuclear factor-kappaB: central regulator in ocular surface inflammation and diseases. The ocular surface 10(3):137–148

    Article  PubMed  Google Scholar 

  63. Bustos-Arriaga J, Garcia-Machorro J, Leon-Juarez M, Garcia-Cordero J, Santos-Argumedo L, Flores-Romo L, Mendez-Cruz AR, Juarez-Delgado FJ, Cedillo-Barron L (2011) Activation of the innate immune response against DENV in normal non-transformed human fibroblasts. PLoS Negl Trop Dis 5(12):e1420

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Decembre E, Assil S, Hillaire ML, Dejnirattisai W, Mongkolsapaya J, Screaton GR, Davidson AD, Dreux M (2014) Sensing of immature particles produced by dengue virus infected cells induces an antiviral response by plasmacytoid dendritic cells. PLoS Pathog 10(10):e1004434

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Cheng F, Yan X, Zhang M, Chang M, Yun S, Meng J, Liu J, Feng CP (2017) Regulation of RAW 264.7 cell-mediated immunity by polysaccharides from Agaricus blazei Murill via the MAPK signal transduction pathway. Food Funct 8(4):1475–1480

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank the members of the Traditional Chinese Veterinary Medicine Laboratory in the College of Veterinary Medicine, Northeast Agricultural University. All authors have read the manuscript and agreed to submit it in its current form for consideration for publication in the journal.

Funding

This work was supported by the National Science Foundation of China (Grant No. 31272533).

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  1. Wanqiu Xie and Ai Lv contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People’s Republic of China

    Wanqiu Xie, Ai Lv, Ruyue Li, Zequn Tang, Dexing Ma, Xiaodan Huang, Ruili Zhang & Ming Ge

  2. Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin, 150030, People’s Republic of China

    Wanqiu Xie, Ai Lv, Ruyue Li, Zequn Tang, Dexing Ma, Xiaodan Huang, Ruili Zhang & Ming Ge

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Correspondence to Ruili Zhang or Ming Ge.

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All procedures used in the current study were approved by the Institutional Animal Care and Use Committee of Northeast Agricultural University in China.

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Xie, W., Lv, A., Li, R. et al. Agaricus blazei Murill Polysaccharides Protect Against Cadmium-Induced Oxidative Stress and Inflammatory Damage in Chicken Spleens. Biol Trace Elem Res 184, 247–258 (2018). https://doi.org/10.1007/s12011-017-1189-6

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