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Toxicological Effect of Manganese on NF-κB/iNOS-COX-2 Signaling Pathway in Chicken Testes

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Abstract

Manganese (Mn) pollution can cause tissue and organ dysfunction and structural damage. The toxicity of Mn in poultry was reported, but inflammatory damage that Mn induced in the testicular tissue has not been reported. The aim of this study was to investigate the effect of Mn poisoning on NF-κB/iNOS-COX-2 signaling pathway in chicken testes. One hundred eighty Hyline male chickens at 7 days of age were fed either commercial diet or MnCl2-added commercial diet containing 600, 900, and 1800 mg/kg Mn for 30, 60, and 90 days, respectively. The messenger RNA (mRNA) expression of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), nitric oxide (NO) content, iNOS activity, and histopathology were examined in chicken testes. The results showed that excess Mn upregulated mRNA expression of NF-κB, COX-2, TNF-α, and iNOS, NO content, and iNOS activity at 60th and 90th day. Mn had a time-dependent effect on NF-κB and TNF-α mRNA expression. Mn had a dose- and time-dependent effect on NO content and iNOS activity. Mn exposure induced chicken testis histological changes in dose- and time-dependent manner. It indicated that Mn exposure resulted in inflammatory injury of chicken testis tissue through NF-κB/iNOS-COX-2 signaling pathway.

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References

  1. Bowman AB, Kwakye GF, Hernández EH, Aschner M (2011) Role of manganese in neurodegenerative diseases. J Trace Elem Med Biol 25(4):191–203. doi:10.1016/j.jtemb.2011.08.144

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Hirayama M, Iijima S, Iwashita M, Akiyama S, Takaku Y, Yamazaki M, Omori T, Yumoto S, Shimamura T (2011) Aging effects of major and trace elements in rat bones and their mutual correlations. J Trace Elem Med Biol 25(2):73–84. doi:10.1016/j.jtemb.2011.02.002

    Article  CAS  PubMed  Google Scholar 

  3. Edina Simon A, Mihály B, Andreas V, Dávid B, István F, Béla T (2011) Air pollution assessment based on elemental concentration of leaves tissue and foliage dust along an urbanization gradient in Vienna. Environ Pollut 159(5):1229–1233. doi:10.1016/j.envpol.2011.01.034

    Article  PubMed  Google Scholar 

  4. Chen T-R, Ke-Fu Y, Li S, Price GJ, Shi Q, Wei G-J (2010) Heavy metal pollution recorded in Porites corals from Daya Bay, northern South China Sea. Mar Environ Res 70(3-4):318–326. doi:10.1016/j.marenvres.2010.06.004

    Article  CAS  PubMed  Google Scholar 

  5. Roels HA, Ghyselen P, Buchet JP, Ceulemans E, Lauwerys RR (1992) Assessment of the permissible exposure level to manganese in workers exposed to manganese dioxide dust. Br J Ind Med 49(1):25–34

    PubMed Central  CAS  PubMed  Google Scholar 

  6. Eun A, Kim H-KC, Joo K-D, Shin J-H, Lee JS, Choi S-B, Myeong-Ok Kim I, Lee J, Kang DM (2007) Effect of manganese exposure on the neuroendocrine system in welders. Neuro Toxicol 28(2):263–269. doi:10.1016/j.neuro.2006.07.013

    Google Scholar 

  7. Ellingsen DG, Konstantinov R, Bast-Pettersen R, Merkurjeva L, Chashchin M, Thomassen Y, Chashchin V (2007) A neurobehavioral study of current and former welders exposed to manganese. Neuro Toxicol 29(1):48–59. doi:10.1016/j.neuro.2007.08.014

    Google Scholar 

  8. Bhang S-Y, Cho S-C, Kim J-W, Hong Y-C, Shin M-S, Yoo HJ, Cho IH, Kimg Y, Kim B-N (2013) Relationship between blood manganese levels and children’s attention, cognition, behavior, and academic performance—a nationwide cross-sectional study. Environ Res 126:9–16. doi:10.1016/j.envres.2013.05.006

    Article  CAS  PubMed  Google Scholar 

  9. Bagga P, Patel AB (2011) Regional cerebral metabolism in mouse under chronic manganese exposure: implications for manganism. Neurochem Int 60(2):177–185. doi:10.1016/j.neuint.2011.10.016

    Article  PubMed  Google Scholar 

  10. Huang P, Chen C, Wang H, Li G, Jing H, Han Y, Liu N, Xiao Y, Qiuhong Y, Liu Y, Wang P, Shi Z, Sun Z (2011) Manganese effects in the liver following subacute or subchronic manganese chloride exposure in rats. Ecotoxicol Environ Saf 74(4):615–622. doi:10.1016/j.ecoenv.2010.08.011

    Article  CAS  PubMed  Google Scholar 

  11. Xiao J, Rui Q, Guo Y, Chang X, Wang D (2008) Prolonged manganese exposure induces severe deficits in lifespan, development and reproduction possibly by altering oxidative stress response in Caenorhabditis elegans. J Environ Sci 21(6):842–848. doi:10.1016/S1001-0742(08)62350-5

    Article  Google Scholar 

  12. Elbetieha A, Bataineh H, Darmani H, Al-Hamood MH (2001) Effects of long-term exposure to manganese chloride on fertility of male and female mice. Toxicol Lett 119(3):193–201

    Article  CAS  PubMed  Google Scholar 

  13. Liu X-f, Zhang L-m, Guan H-n, Zhang Z-w, Shi-wen X (2013) Effects of oxidative stress on apoptosis in manganese-induced testicular toxicity in cocks. Food Chem Toxicol 60:168–176. doi:10.1016/j.fct.2013.07.058

    Article  CAS  PubMed  Google Scholar 

  14. Chen C-J, Yen-Chuan O, Lin S-Y, Liao S-L, Chen S-Y, Chen J-H (2006) Manganese modulates pro-inflammatory gene expression in activated glia. Neurochem Int 49(1):62–71. doi:10.1016/j.neuint.2005.12.020

    Article  CAS  PubMed  Google Scholar 

  15. Liang Y, Zhou Y, Shen P (2004) NF-κB and its regulation on the immune system. Cell Mol Immunol 1(5):343–350

    CAS  PubMed  Google Scholar 

  16. Clària J (2003) Cyclooxygenase-2 biology. Curr Pharm Des 9(27):2177–2190

    Article  PubMed  Google Scholar 

  17. Lawrence T (2009) The nuclear factor NF-κB pathway in inflammation. Cold Spring Harb Perspect Biol 1(6):a001651. doi:10.1101/cshperspect.a001651

    Article  PubMed Central  PubMed  Google Scholar 

  18. Kim SF, Huri DA, Snyder SH (2005) Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2. Science 310(5756):1966–1970. doi:10.1126/science.1119407

    Article  CAS  PubMed  Google Scholar 

  19. Bogdan C (2001) Nitric oxide and the immune response. Nat Immunol 2(10):907–916. doi:10.1038/ni1001-907

    Article  CAS  PubMed  Google Scholar 

  20. Moncada S (1999) Nitric oxide: discovery and impact on clinical medicine. J R Soc Med 92(4):164–169

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Shao J-J, Yao H-D, Zhang Z-W, Li S, Shi-Wen X (2012) The disruption of mitochondrial metabolism and ion homeostasis in chicken hearts exposed to manganese. Toxicol Lett 214(2):99–108. doi:10.1016/j.toxlet.2012.08.011

    Article  CAS  PubMed  Google Scholar 

  22. Liu X, Li Z, Han C, Zhang Z, Shiwen X (2012) Effects of dietary manganese on Cu, Fe, Zn, Ca, Se, IL-1β, and IL-2 changes of immune organs in cocks. Biol Trace Elem Res 148(3):336–344. doi:10.1007/s12011-012-9377-x

    Article  CAS  PubMed  Google Scholar 

  23. Zhu Y, Xinxing L, Di W, Cai S, Li S, Teng X (2013) The effect of manganese-induced cytotoxicity on mRNA expressions of HSP27, HSP40, HSP60, HSP70 and HSP90 in chicken spleen lymphocytes in vitro. Biol Trace Elem Res 156(1–3):144–152. doi:10.1007/s12011-013-9817-2

    Article  CAS  PubMed  Google Scholar 

  24. Curtis Klaassen (2007) Casarett & Doull’s Toxicology: The basic science of poisons. McGraw-Hill

  25. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45. doi:10.1093/nar/29.9.e45

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Aktan F (2004) iNOS-mediated nitric oxide production and its regulation. Life Sci 75(6):639–653. doi:10.1016/j.lfs.2003.10.042

    Article  CAS  PubMed  Google Scholar 

  27. Sharma JN, Al-Omran A, Parvathy SS (2007) Role of nitric oxide in inflammatory diseases. Inflammopharmacology 15(6):252–259. doi:10.1007/s10787-007-0013-x

    Article  CAS  PubMed  Google Scholar 

  28. Zhang F, Chen L, Liu C, Qiu P, Wang A, Li L, Wang H (2013) Up-regulation of protein tyrosine nitration in methamphetamine-induced neurotoxicity through DDAH/ADMA/NOS pathway. Neurochem Int 62(8):1055–1064. doi:10.1016/j.neuint.2013.03.016

    Article  CAS  PubMed  Google Scholar 

  29. Wei Q, Li J, Li X, Zhang L, Shi F (2014) Reproductive toxicity in acrylamide-treated female mice. Reprod Toxicol 46:121–128. doi:10.1016/j.reprotox.2014.03.007

    Article  CAS  PubMed  Google Scholar 

  30. Liu X, Zuo N, Guan H, Han C, Shi Wen X (2013) Manganese-induced effects on cerebral trace element and nitric oxide of Hyline cocks. Biol Trace Elem Res 154(2):202–209. doi:10.1007/s12011-013-9692-x

    Article  CAS  PubMed  Google Scholar 

  31. Turgut G, Abban G, Turgut S, Take G (2003) Effect of overdose zinc on mouse testis and its relation with sperm count and motility. Biol Trace Elem Res 96(1–3):271–279

    Article  CAS  PubMed  Google Scholar 

  32. Zhang D-Y, Shen X-Y, Ruan Q, Xiao-Lu X, Yang S-P, Lua Y, Hui-Ying X, Hao F-L (2014) Effects of subchronic samarium exposure on the histopathological structure and apoptosis regulation in mouse testis. Environ Toxicol Pharmacol 37(2):505–512. doi:10.1016/j.etap.2014.01.007

    Article  CAS  PubMed  Google Scholar 

  33. Bastian H, Schmid JA (2013) The complexity of NF-κB signaling in inflammation and cancer. Molecular Cancer 12:86. doi:10.1186/1476-4598-12-86

    Article  Google Scholar 

  34. Tak PP, Firestein GS (2001) NF-κB: a key role in inflammatory diseases. J Clin Invest 107(1):7–11

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Xing D, Feng W, Miller AP, Weathington NM, Chen Y-F, Lea N, Edwin Blalock J, Opari S (2007) Estrogen modulates TNF-α-induced inflammatory responses in rat aortic smooth muscle cells through estrogen receptor-β activation. Am J Physiol Heart Circ Physiol 292(6):H2607–H2612. doi:10.1152/ajpheart.01107.2006

    Article  CAS  PubMed  Google Scholar 

  36. Ricciotti E, FitzGerald GA (2011) Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31(5):986–1000. doi:10.1161/ATVBAHA.110.207449

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Bilen S, Biswas G, Otsuyama S, Kono T, Sakai M, Hikima J-i (2014) Inflammatory responses in the Japanese pufferfish (Takifugu rubripes) head kidney cells stimulated with an inflammasome-inducing agent, nigericin. Dev Comp Immunol 46(2):222–230. doi:10.1016/j.dci.2014.04.010

    Article  CAS  PubMed  Google Scholar 

  38. Li R, Kou X, Tian J, Meng Z, Cai Z, Cheng F, Dong C (2014) Effect of sulfur dioxide on inflammatory and immune regulation in asthmatic rats. Chemosphere 112:296–304. doi:10.1016/j.chemosphere.2014.04.065

    Article  CAS  PubMed  Google Scholar 

  39. Jia Z, Liu M, Zhe Q, Zhang Y, Yin S, Shan A (2014) Toxic effects of zearalenone on oxidative stress, inflammatory cytokines, biochemical and pathological changes induced by this toxin in the kidney of pregnant rats. Environ Toxicol Pharmacol 37(2):580–591. doi:10.1016/j.etap.2014.01.010

    Article  CAS  PubMed  Google Scholar 

  40. Wan L-YM, Woo C-SJ, Turner PC, Wan JM-F, El-Nezami H (2013) Individual and combined effects of Fusarium toxins on the mRNA expression of pro-inflammatory cytokines in swine jejunal epithelial cells. Toxicol Lett 220(3):238–246. doi:10.1016/j.toxlet.2013.05.003

    Article  CAS  PubMed  Google Scholar 

  41. Leite CE, de Oliveira L, Maboni FF, Cruz DB, Rosemberg FF, Zimmermann TC, Pereira B, Bogo MR, Bonan CD, Campos MM, Morrone FB, Battastini AMO (2013) Involvement of purinergic system in inflammation and toxicity induced by copper in zebrafish larvae. Toxicol Appl Pharmacol 272(3):681–689. doi:10.1016/j.taap.2013.08.001

    Article  CAS  PubMed  Google Scholar 

  42. Park E-J, Park K (2009) Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro. Toxicol Lett 184(1):18–25. doi:10.1016/j.toxlet.2008.10.012

    Article  CAS  PubMed  Google Scholar 

  43. Medeiros R, Rui DS, Prediger GF, Passos PP, Duarte FS, Franco JL, Dafre AL, Di Giunta G, Figueiredo CP, Takahashi RN, Campos MM, Calixto JB (2007) Connecting TNF-α signaling pathways to iNOS expression in a mouse model of Alzheimer’s disease: relevance for the behavioral and synaptic deficits induced by amyloid β protein. J Neurosci 27(20):5394–5404. doi:10.1523/JNEUROSCI.5047-06.2007

    Article  CAS  PubMed  Google Scholar 

  44. Atiqur Rahman M, Dipok Kumar D, Emi Y, Seiji M, Takashi S, Hikota H, Takashi O, Akira Y, Hitoshi K, Naofumi N (2001) Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases. Clin Cancer Res 7(5):1325–1332

    Google Scholar 

  45. Charalambous MP, Lightfoot T, Speirs V, Horgan K, Gooderham NJ (2009) Expression of COX-2, NF-κB-p65, NF-κB-p50 and IKKα in malignant and adjacent normal human colorectal tissue. Br J Cancer 101(1):106–115. doi:10.1038/sj.bjc.6605120

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Elizabeth MA, Hasan H, George F, Zak E, Sam S-H, Christine D, Anthony Paul G, John B, Jenkins GJ (2012) Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) are important mediators of reflux induced cell signalling in esophageal cells. Carcinogenesis 33(11):2035–2043. doi:10.1093/carcin/bgs241

    Article  Google Scholar 

  47. Caamaño J, Hunter CA (2002) NF-κB family of transcription factors: central regulators of innate and adaptive immune functions. Clin Microbiol Rev 15(3):414–429. doi:10.1128/CMR.15.3.414-429.2002

    Article  PubMed Central  PubMed  Google Scholar 

  48. Chen C-C, Sun Y-T, Chen J-J, Chiu K-T (2000) TNF-alpha-induced cyclooxygenase-2 expression in human lung epithelial cells: involvement of the phospholipase C-gamma 2, protein kinase C-alpha, tyrosine kinase, NF-kappa B-inducing kinase, and I-kappa B kinase 1/2 pathway. J Immunol 165(5):2719–2728

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank the Doctoral Program Foundation of Institutions of Institutions of Higher Education of China (No. 2010RCB32) and the Heilongjiang Province on the Natural Fund Project (41400172-4-14089).

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Correspondence to Xiaohua Teng or Shu Li.

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Du, Y., Zhu, Y., Teng, X. et al. Toxicological Effect of Manganese on NF-κB/iNOS-COX-2 Signaling Pathway in Chicken Testes. Biol Trace Elem Res 168, 227–234 (2015). https://doi.org/10.1007/s12011-015-0340-5

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