Skip to main content
Log in

Arsenic Trioxide Attenuates NF-κB and Cytokine mRNA Levels in the Livers of Cocks

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Arsenic (As) is a trace element widely found in nature. It exists in several forms, including organic arsenic, inorganic arsenic, and trivalent arsenic, the most toxic. Arsenic trioxide (As2O3) is widespread in nature. This form tends to accumulate in animals and humans and therefore has a potential harm for them. Cytokines play essential roles in the immune response and inflammation. Although the importance of cytokines in the responses to arsenic exposure has been demonstrated in many types of mammals, the function of these in poultry, especially in chickens, remains unclear. The purpose of the present study was to examine the effect of As2O3 exposure on cytokines in cock livers. In this study, 72 1-day-old male Hy-line cocks were randomly divided into four groups including the control group, low-As group, middle-As group, and high-As group. The livers were collected on days 30, 60, and 90 of the experiment. The levels of nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 beta (IL-12β), and interleukin-1 beta (IL-1β) mRNA in the livers of the cocks were measured using real-time PCR. The results showed that the expression levels of IL-6, IL-8, TNF-α, and NF-κB which seemed to be a critical mediator in the inflammatory response tended to increase in the birds chronically treated with As2O3. However, the mRNA expression levels of IL-4, IL-12β, and IL-1β were decreased in the experiment. The information regarding the effects of As2O3 on cytokine mRNA expression generated in this study will be important information for arsenic toxicology evaluation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Hall JC, Harruff R (1989) Fatal cardiac arrhythmia in a patient with interstitial myocarditis related to chronic arsenic poisoning. South Med J 82:1557–60

    Article  CAS  PubMed  Google Scholar 

  2. Walvekar RR, Kane SV, Nadkarni MS, Bagwan IN, Chaukar DA, D’Cruz AK (2007) Chronic arsenic poisoning: a global health issue—a report of multiple primary cancers. J Cutan Pathol 34:203–6

    Article  CAS  PubMed  Google Scholar 

  3. Pi J, Kumagai Y, Sun G, Yamauchi H, Yoshida T, Iso H, Endo A, Yu L, Yuki K, Miyauchi T, Shimojo N (2000) Decreased serum concentrations of nitric oxide metabolites among Chinese in an endemic area of chronic arsenic poisoning in inner Mongolia. Free Radic Biol Med 28:1137–42

    Article  CAS  PubMed  Google Scholar 

  4. Bhadauria S, Flora SJ (2007) Response of arsenic-induced oxidative stress, DNA damage, and metal imbalance to combined administration of DMSA and monoisoamyl-DMSA during chronic arsenic poisoning in rats. Cell Biol Toxicol 23:91–104

    Article  CAS  PubMed  Google Scholar 

  5. Flora SJ (1999) Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3-dimercaptosuccinic acid in rats. Clin Exp Pharmacol Physiol 26:865–9

    Article  CAS  PubMed  Google Scholar 

  6. Fowler BA, Woods JS, Schiller CM (1977) Ultrastructural and biochemical effects of prolonged oral arsenic exposure on liver mitochondria of rats. Environ Health Perspect 19:197–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dick L, Parker LA, Mauro MA (1990) Chronic arsenic poisoning as a cause of increased hepatic density with CT. J Comput Assist Tomogr 14:828–9

    Article  CAS  PubMed  Google Scholar 

  8. Santra A, Maiti A, Das S, Lahiri S, Charkaborty SK, Mazumder DN (2000) Hepatic damage caused by chronic arsenic toxicity in experimental animals. J Toxicol Clin Toxicol 38:395–405

    Article  CAS  PubMed  Google Scholar 

  9. Epanchintsev A, Shyamsunder P, Verma RS, Lyakhovich A (2014) IL-6, IL-8, MMP-2, MMP-9 are overexpressed in Fanconi anemia cells through a NF-kappaB/TNF-alpha dependent mechanism. Mol Carcinog 14:1–14

  10. Fu J, Liu CP, Zhang ZW, Xing MW, Xu SW (2013) Influence of inflammatory pathway markers on oxidative stress induced by cold stress in intestine of quails. Res Vet Sci 95:495–501

    Article  CAS  PubMed  Google Scholar 

  11. Dangleben NL, Skibola CF, Smith MT (2013) Arsenic immunotoxicity: a review. Environ Health 12:73

    Article  PubMed  PubMed Central  Google Scholar 

  12. Piamphongsant T (1999) Chronic environmental arsenic poisoning. Int J Dermatol 38:401–10

    Article  CAS  PubMed  Google Scholar 

  13. Ahmed S, Mahabbat-e KS, Rekha RS, Gardner RM, Ameer SS, Moore S, Ekström EC, Vahter M, Raqib R (2011) Arsenic-associated oxidative stress, inflammation, and immune disruption in human placenta and cord blood. Environ Health Perspect 119:258–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ghosh S, Hayden MS (2008) New regulators of NF-kappaB in inflammation. Nat Rev Immunol 8:837–48

    Article  CAS  PubMed  Google Scholar 

  15. Thanos D, Maniatis T (1995) NF-kappa B: a lesson in family values. Cell 80:529–32

    Article  CAS  PubMed  Google Scholar 

  16. Zhang W, Zhang R, Wang T, Jiang H, Guo M, Zhou E, Sun Y, Yang Z, Xu S, Cao Y, Zhang N (2014) Selenium inhibits LPS-induced pro-inflammatory gene expression by modulating MAPK and NF-kappaB signaling pathways in mouse mammary epithelial cells in primary culture. Inflammation 37:478–85

    Article  CAS  PubMed  Google Scholar 

  17. Peters BA, Liu X, Hall MN, Ilievski V, Slavkovich V, Siddique AB, Alam S, Islam T, Graziano JH, Gamble MV (2015) Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential. Free Radic Biol Med 85:174–82

    Article  CAS  PubMed  Google Scholar 

  18. Xu Z, Wang Z, Li JJ, Chen C, Zhang PC, Dong L, Chen JH, Chen Q, Zhang XT, Wang ZL (2013) Protective effects of selenium on oxidative damage and oxidative stress related gene expression in rat liver under chronic poisoning of arsenic. Food Chem Toxicol 58:1–7

    Article  CAS  PubMed  Google Scholar 

  19. Niyazoglu M, Baykara O, Koc A, Aydogdu P, Onaran I, Dellal FD, Tasan E, Sultuybek GK (2014) Association of PARP-1, NF-kappaB, NF-kappaBIA and IL-6, IL-1beta and TNF-alpha with Graves Disease and Graves Ophthalmopathy. Gene 547:226–32

    Article  CAS  PubMed  Google Scholar 

  20. Zhao FQ, Zhang ZW, Wang C, Zhang B, Yao HD, Li S, Xu SW (2013) The role of heat shock proteins in inflammatory injury induced by cold stress in chicken hearts. Cell Stress Chaperones 18:773–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Arican O, Aral M, Sasmaz S, Ciragil P (2005) Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm 5:273–9

  22. Ehrenstein MR, Evans JG, Singh A, Moore S, Warnes G, Isenberg DA, Mauri C (2004) Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med 200:277–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhu T, Zhang L, Ling S, Duan J, Qian F, Li Y, Xu JW (2014) Scropolioside B inhibits IL-1beta and cytokines expression through NF-kappaB and inflammasome NLRP3 pathways. Mediators Inflamm 2014:819053

    Article  PubMed  PubMed Central  Google Scholar 

  24. Liu X, Ye F, Xiong H, Hu DN, Limb GA, Xie T, Peng L, Zhang P, Wei Y, Zhang W, Wang J, Wu H, Lee P, Song E, Zhang DY (2015) IL-1beta induces IL-6 production in retinal Muller cells predominantly through the activation of p38 MAPK/NF-kappaB signaling pathway. Exp Cell Res 331:223–31

    Article  CAS  PubMed  Google Scholar 

  25. Ma Z, Piao T, Wang Y, Liu J (2015) Astragalin inhibits IL-1beta-induced inflammatory mediators production in human osteoarthritis chondrocyte by inhibiting NF-kappaB and MAPK activation. Int Immunopharmacol 25:83–7

    Article  CAS  PubMed  Google Scholar 

  26. Adelibieke Y, Yisireyili M, Ng HY, Saito S, Nishijima F, Niwa T (2014) Indoxyl sulfate induces IL-6 expression in vascular endothelial and smooth muscle cells through OAT3-mediated uptake and activation of AhR/NF-kappaB pathway. Nephron Exp Nephrol 128:1–8

    Article  CAS  PubMed  Google Scholar 

  27. Warner N, Burberry A, Pliakas M, McDonald C, Nunez G (2014) A genome-wide small interfering RNA (siRNA) screen reveals nuclear factor-kappaB (NF-kappaB)-independent regulators of NOD2-induced interleukin-8 (IL-8) secretion. J Biol Chem 289:28213–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kassi E, Chinou I, Spilioti E, Tsiapara A, Graikou K, Karabournioti S, Manoussakis M, Moutsatsou P (2014) A monoterpene, unique component of thyme honeys, induces apoptosis in prostate cancer cells via inhibition of NF-kappaB activity and IL-6 secretion. Phytomedicine 21:1483–9

    Article  CAS  PubMed  Google Scholar 

  29. Yang H, Qi H, Ren J, Cui J, Li Z, Waldum HL, Cui G (2014) Involvement of NF-kappaB/IL-6 pathway in the processing of colorectal carcinogenesis in colitis mice. Int J Inflam 2014:130981

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chen D, Zhang Z, Yao H, Cao Y, Xing H, Xu S (2014) Pro- and anti-inflammatory cytokine expression in immune organs of the common carp exposed to atrazine and chlorpyrifos. Pestic Biochem Physiol 114:8–15

    Article  CAS  PubMed  Google Scholar 

  31. Cho JS, Han IH, Lee HR, Lee HM (2014) Prostaglandin E2 induces IL-6 and IL-8 production by the EP receptors/Akt/NF-kappaB pathways in nasal polyp-derived fibroblasts. Allergy Asthma Immunol Res 6:449–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Duan D, Zhang S, Li X, Guo H, Chen M, Zhang Y, Han J, Lv Y (2014) Activation of the TLR/MyD88/NF-kappaB signal pathway contributes to changes in IL-4 and IL-12 production in piglet lymphocytes infected with porcine circovirus type 2 in vitro. PLoS One 9:e97653

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by the Postdoctoral Scientific-Research Developmental Foundation of Heilongjiang Province (Grant No. LBH-Q13012) and Heilongjiang Province Natural Science Foundation (Grant No. C2015061).

Conflict of Interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Wen Zhang or Mingwei Xing.

Additional information

Kexin Zhang and Panpan Zhao contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, K., Zhao, P., Guo, G. et al. Arsenic Trioxide Attenuates NF-κB and Cytokine mRNA Levels in the Livers of Cocks. Biol Trace Elem Res 170, 432–437 (2016). https://doi.org/10.1007/s12011-015-0455-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-015-0455-8

Keywords

Navigation