Skip to main content

Advertisement

Log in

Protective Roles of Selenium on Nitric Oxide-Mediated Apoptosis of Immune Organs Induced by Cadmium in Chickens

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

Abstract

Little is known about the influence of subchronic cadmium exposure on apoptosis in the immune organs of birds and the protective effects on apoptosis by selenium against cadmium. The aim of this study was to investigate the effect of subchronic cadmium exposure on nitric oxide and apoptosis in the immune organs of chicken and the protective roles of selenium against cadmium-induced apoptosis. Two hundred ten 30-day-old chickens were randomly assigned to three groups and were fed a basal diet, cadmium + selenium (as 150 mg of CdCl2 per kg of diet + 10 mg of Na2SeO3 per kg of diet ) or cadmium (as 150 mg of CdCl2 per kg of diet) in basic diets for 15, 30, 45, and 60 days. Then, the production of nitric oxide, messenger RNA (mRNA level), and the activity of inducible nitric oxide synthase, ultrastructural changes, TUNEL assay, and flow cytometric analysis of apoptosis and Bcl-2 and p53 mRNA levels in the immune organs were examined. The results showed that cadmium exposure caused ultrastructural damage and increased production of nitric oxide, mRNA level, and activity of inducible nitric oxide synthase, the degree, and the number of apoptotic cells in a time-dependent manner. Cadmium exposure decreased Bcl-2 mRNA level and increased p53 mRNA level in a time-dependent manner. Selenium supplementation during dietary cadmium reduced the production of nitric oxide, the mRNA level, and activity of inducible nitric oxide synthase, ultrastructural damage, and apoptosis in the immune organs of chicken. It indicated that cadmium induced nitric oxide-mediated apoptosis of immune organs, and selenium played protective effects against cadmium-induced apoptosis in the immune organs of chickens.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Ferramola ML, Perez Diaz MF, Honore SM, Sanchez SS, Anton RI, Anzulovich AC, Gimenez MS (2012) Cadmium-induced oxidative stress and histological damage in the myocardium. Effects of a soy-based diet. Toxicol Appl Pharmacol 265(3):380–389

    Article  CAS  PubMed  Google Scholar 

  2. Lazarus M, Orct T, Aladrovic J, Ljubic BB, Jurasovic J, Blanusa M (2011) Effect of selenium pre-treatment on antioxidative enzymes and lipid peroxidation in Cd-exposed suckling rats. Biol Trace Elem Res 142(3):611–622

    Article  CAS  PubMed  Google Scholar 

  3. Messaoudi I, El Heni J, Hammouda F, Said K, Kerkeni A (2009) Protective effects of selenium, zinc, or their combination on cadmium-induced oxidative stress in rat kidney. Biol Trace Elem Res 130(2):152–161

    Article  CAS  PubMed  Google Scholar 

  4. Hemdan NY, Emmrich F, Sack U, Wichmann G, Lehmann J, Adham K, Lehmann I (2006) The in vitro immune modulation by cadmium depends on the way of cell activation. Toxicology 222(1–2):37–45

    Article  CAS  PubMed  Google Scholar 

  5. Hanson ML, Holaskova I, Elliott M, Brundage KM, Schafer R, Barnett JB (2012) Prenatal cadmium exposure alters postnatal immune cell development and function. Toxicol Appl Pharmacol 261(2):196–203

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Pathak N, Khandelwal S (2009) Immunomodulatory role of piperine in cadmium induced thymic atrophy and splenomegaly in mice. Environ Toxicol Pharmacol 28(1):52–60

    Article  CAS  PubMed  Google Scholar 

  7. Pathak N, Khandelwal S (2007) Role of oxidative stress and apoptosis in cadmium induced thymic atrophy and splenomegaly in mice. Toxicol Lett 169(2):95–108

    Article  CAS  PubMed  Google Scholar 

  8. Chatterjee S, Kundu S, Bhattacharyya A (2008) Mechanism of cadmium induced apoptosis in the immunocyte. Toxicol Lett 177(2):83–89

    Article  CAS  PubMed  Google Scholar 

  9. Fouad AA, Jresat I (2014) Thymoquinone therapy abrogates toxic effect of cadmium on rat testes. Andrologia. doi:10.1111/and.12281

    PubMed  Google Scholar 

  10. Chen L, Zhou J, Gao W, Jiang YZ (2003) Action of NO and TNF-alpha release of rats with cadmium loading in malfunctiion of multiple system organ. Sheng Li Xue Bao 55(5):535–540

    CAS  PubMed  Google Scholar 

  11. Chaturvedi R, Asim M, Hoge S, Lewis ND, Singh K, Barry DP, de Sablet T, Piazuelo MB, Sarvaria AR, Cheng Y, Closs EI, Casero RA, Jr., Gobert AP, Wilson KT (2010) Polyamines impair immunity to Helicobacter pylori by inhibiting L-arginine uptake required for nitric oxide production. Gastroenterology 139 (5):1686-1698, 1698 e1681-1686

  12. Razavi HM, Hamilton JA, Feng Q (2005) Modulation of apoptosis by nitric oxide: implications in myocardial ischemia and heart failure. Pharmacol Ther 106(2):147–162

    Article  CAS  PubMed  Google Scholar 

  13. Bai F, Ni B, Liu M, Feng Z, Xiong Q, Xiao S, Shao G (2013) Mycoplasma hyopneumoniae-derived lipid-associated membrane proteins induce apoptosis in porcine alveolar macrophage via increasing nitric oxide production, oxidative stress, and caspase-3 activation. Vet Immunol Immunopathol 155(3):155–161

    Article  CAS  PubMed  Google Scholar 

  14. Ilmarinen-Salo P, Moilanen E, Kinnula VL, Kankaanranta H (2012) Nitric oxide-induced eosinophil apoptosis is dependent on mitochondrial permeability transition (mPT), JNK and oxidative stress: apoptosis is preceded but not mediated by early mPT-dependent JNK activation. Respir Res 13:73

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Zhou JL, Fang HS, Peng H, Hu QJ, Liu SQ, Ming JH, Qiu B (2013) PKCa agonists enhance the protective effect of hyaluronic acid on nitric oxide-induced apoptosis of articular chondrocytes in vitro. Iran J Basic Med Sci 16(12):1276–1281

    PubMed Central  PubMed  Google Scholar 

  16. Fischer JL, Lancia JK, Mathur A, Smith ML (2006) Selenium protection from DNA damage involves a Ref1/p53/Brca1 protein complex. Anticancer Res 26(2A):899–904

    CAS  PubMed  Google Scholar 

  17. Bansal MP, Kaur P (2005) Selenium, a versatile trace element: current research implications. Indian J Exp Biol 43(12):1119–1129

    CAS  PubMed  Google Scholar 

  18. Abarikwu SO, Iserhienrhien BO, Badejo TA (2013) Rutin- and selenium-attenuated cadmium-induced testicular pathophysiology in rats. Hum Exp Toxicol 32(4):395–406

    Article  CAS  PubMed  Google Scholar 

  19. Liu LL, Li CM, Zhang ZW, Zhang JL, Yao HD, Xu SW (2014) Protective effects of selenium on cadmium-induced brain damage in chickens. Biol Trace Elem Res 158(2):176–185

    Article  CAS  PubMed  Google Scholar 

  20. Ayaz M, Turan B (2006) Selenium prevents diabetes-induced alterations in [Zn2+]i and metallothionein level of rat heart via restoration of cell redox cycle. Am J Physiol Heart Circ Physiol 290(3):H1071–H1080

    Article  CAS  PubMed  Google Scholar 

  21. Yun CH, Yang JS, Kang SS, Yang Y, Cho JH, Son CG, Han SH (2007) NF-kappaB signaling pathway, not IFN-beta/STAT1, is responsible for the selenium suppression of LPS-induced nitric oxide production. Int Immunopharmacol 7(9):1192–1198

    Article  CAS  PubMed  Google Scholar 

  22. Zhou YJ, Zhang SP, Liu CW, Cai YQ (2009) The protection of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium-induced LLC-PK(1) cells. Toxicol In Vitro 23(2):288–294

    Article  PubMed  Google Scholar 

  23. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. Pathak N, Khandelwal S (2006) Oxidative stress and apoptotic changes in murine splenocytes exposed to cadmium. Toxicology 220(1):26–36

    Article  CAS  PubMed  Google Scholar 

  26. Kao XB, Gao Y, Chen JH, Chen Q, Wang ZL, Wang Z (2013) Role of JNK signaling pathway in chondrocyte apoptosis induced by nitric oxide. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 31(4):271–275

    CAS  PubMed  Google Scholar 

  27. Ilmarinen-Salo P, Moilanen E, Kankaanranta H (2010) Nitric oxide induces apoptosis in GM-CSF-treated eosinophils via caspase-6-dependent lamin and DNA fragmentation. Pulm Pharmacol Ther 23(4):365–371

    Article  CAS  PubMed  Google Scholar 

  28. Park MY, Jeong YJ, Kang GC, Kim MH, Kim SH, Chung HJ, Jung JY, Kim WJ (2014) Nitric oxide-induced apoptosis of human dental pulp cells is mediated by the mitochondria-dependent pathway. Korean J Physiol Pharmacol 18(1):25–32

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Baronetti JL, Villegas NA, Paraje MG, Albesa I (2011) Nitric oxide-mediated apoptosis in rat macrophages subjected to Shiga toxin 2 from Escherichia coli. Microbiol Immunol 55(4):231–238

    Article  CAS  PubMed  Google Scholar 

  30. Hu ZY, Cheng SM, Zhu QX (2006) Influence of induced nitric oxide synthase expression on apoptosis of thymocyte in burn rats. Zhonghua Shao Shang Za Zhi 22(6):419–422

    CAS  PubMed  Google Scholar 

  31. Soyupek S, Oksay T, Sutcu R, Armagan A, Gokalp O, Perk H, Delibas N (2012) The effect of cadmium toxicity on renal nitric oxide synthase isoenzymes. Toxicol Ind Health 28(7):624–628

    Article  CAS  PubMed  Google Scholar 

  32. Ramirez DC, Gimenez MS (2003) Induction of redox changes, inducible nitric oxide synthase and cyclooxygenase-2 by chronic cadmium exposure in mouse peritoneal macrophages. Toxicol Lett 145(2):121–132

    Article  CAS  PubMed  Google Scholar 

  33. Yang S, Zhang Z, He J, Li J, Zhang J, Xing H, Xu S (2012) Ovarian toxicity induced by dietary cadmium in hen. Biol Trace Elem Res 148(1):53–60

    Article  CAS  PubMed  Google Scholar 

  34. Giovannetti A, Pierdominici M, Di Iorio A, Cianci R, Murdaca G, Puppo F, Pandolfi F, Paganelli R (2008) Apoptosis in the homeostasis of the immune system and in human immune mediated diseases. Curr Pharm Des 14(3):253–268

    Article  CAS  PubMed  Google Scholar 

  35. Shi X, LeCapitaine NJ, Rudner XL, Ruan S, Shellito JE (2009) Lymphocyte apoptosis in murine Pneumocystis pneumonia. Respir Res 10:57

    Article  PubMed Central  PubMed  Google Scholar 

  36. Zhou Z, Wang C, Liu H, Huang Q, Wang M, Lei Y (2013) Cadmium induced cell apoptosis, DNA damage, decreased DNA repair capacity, and genomic instability during malignant transformation of human bronchial epithelial cells. Int J Med Sci 10(11):1485–1496

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Murugavel P, Pari L, Sitasawad SL, Kumar S, Kumar S (2007) Cadmium induced mitochondrial injury and apoptosis in vero cells: protective effect of diallyl tetrasufide from garlic. Int J Biochem Cell Biol 39(1):161–170

    Article  CAS  PubMed  Google Scholar 

  38. Al-Assaf AH, Alqahtani AM, Alshatwi AA, Syed NA, Shafi G, Hasan TN (2013) Mechanism of cadmium induced apoptosis in human peripheral blood lymphocytes: the role of p53, Fas and Caspase-3. Environ Toxicol Pharmacol 36(3):1033–1039

    Article  CAS  PubMed  Google Scholar 

  39. Desagher S, Martinou JC (2000) Mitochondria as the central control point of apoptosis. Trends Cell Biol 10(9):369–377

    Article  CAS  PubMed  Google Scholar 

  40. Bruce-Keller AJ, Begley JG, Fu W, Butterfield DA, Bredesen DE, Hutchins JB, Hensley K, Mattson MP (1998) Bcl-2 protects isolated plasma and mitochondrial membranes against lipid peroxidation induced by hydrogen peroxide and amyloid beta-peptide. J Neurochem 70(1):31–39

    Article  CAS  PubMed  Google Scholar 

  41. Li YZ, Lu DY, Tan WQ, Wang JX, Li PF (2008) p53 initiates apoptosis by transcriptionally targeting the antiapoptotic protein ARC. Mol Cell Biol 28(2):564–574

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, Moll UM (2003) p53 has a direct apoptogenic role at the mitochondria. Mol Cell 11(3):577–590

    Article  CAS  PubMed  Google Scholar 

  43. Yiran Z, Chenyang J, Jiajing W, Yan Y, Jianhong G, Jianchun B, Xuezhong L, Zongping L (2013) Oxidative stress and mitogen-activated protein kinase pathways involved in cadmium-induced BRL 3A cell apoptosis. Oxid Med Cell Longev 2013:516051

    Article  PubMed Central  PubMed  Google Scholar 

  44. Son YO, Lee JC, Hitron JA, Pan J, Zhang Z, Shi X (2010) Cadmium induces intracellular Ca2+- and H2O2-dependent apoptosis through JNK- and p53-mediated pathways in skin epidermal cell line. Toxicol Sci 113(1):127–137

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Yu X, Sidhu JS, Hong S, Robinson JF, Ponce RA, Faustman EM (2011) Cadmium induced p53-dependent activation of stress signaling, accumulation of ubiquitinated proteins, and apoptosis in mouse embryonic fibroblast cells. Toxicol Sci 120(2):403–412

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Qin F, Zhu X, Zhang W, Zhou J, Zhang S, Jia Z (2011) Effects of dietary iodine and selenium on nutrient digestibility, serum thyroid hormones, and antioxidant status of Liaoning cashmere goats. Biol Trace Elem Res 143(3):1480–1488

    Article  CAS  PubMed  Google Scholar 

  47. Maldonado PD, Perez-De La Cruz V, Torres-Ramos M, Silva-Islas C, Lecona-Vargas R, Lugo-Huitron R, Blanco-Ayala T, Ugalde-Muniz P, Vazquez-Cervantes GI, Fortoul TI, Ali SF, Santamaria A (2012) Selenium-induced antioxidant protection recruits modulation of thioredoxin reductase during excitotoxic/pro-oxidant events in the rat striatum. Neurochem Int 61(2):195–206

    Article  CAS  PubMed  Google Scholar 

  48. Zhang ZW, Zhang JL, Gao YH, Wang QH, Li S, Wang XL, Xu SW (2013) Effect of oxygen free radicals and nitric oxide on apoptosis of immune organ induced by selenium deficiency in chickens. Biometals 26(2):355–365

    Article  CAS  PubMed  Google Scholar 

  49. Sheng PF, Jiang Y, Zhang ZW, Zhang JL, Li S, Zhang ZQ, Xu SW (2014) The effect of Se-deficient diet on gene expression of inflammatory cytokines in chicken brain. Biometals 27(1):33–43

    Article  CAS  PubMed  Google Scholar 

  50. Ognjanovic BI, Markovic SD, Pavlovic SZ, Zikic RV, Stajn AS, Saicic ZS (2008) Effect of chronic cadmium exposure on antioxidant defense system in some tissues of rats: protective effect of selenium. Physiol Res 57(3):403–411

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  52. Wang Y, Wu Y, Luo K, Liu Y, Zhou M, Yan S, Shi H, Cai Y (2013) The protective effects of selenium on cadmium-induced oxidative stress and apoptosis via mitochondria pathway in mice kidney. Food Chem Toxicol 58:61–67

    Article  CAS  PubMed  Google Scholar 

  53. Chen HJ, Yu RA, Wu ZG, Xia T, Yang CF, Yang KD, Chen XM (2006) Effects of selenium on expression of TERT, c-Myc and p53 induced by cadmium in rat liver. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 24(1):35–38

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank the members of the Veterinary Internal Medicine Laboratory in the College of Veterinary Medicine, Northeast Agricultural University, and special thanks to the members of the Cd-diet group for the help they supplied in the research. This work was supported by Bureau of Education of Heilongjiang Province (No. 10551038).

Conflict of Interest

All authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Gang Sun or Shi-wen Xu.

Additional information

All other authors have read the manuscript and have agreed to submit it in its current form for consideration for publication in the Journal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Ll., Zhang, Jl., Zhang, Zw. et al. Protective Roles of Selenium on Nitric Oxide-Mediated Apoptosis of Immune Organs Induced by Cadmium in Chickens. Biol Trace Elem Res 159, 199–209 (2014). https://doi.org/10.1007/s12011-014-0007-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-0007-7

Keywords

Navigation