Biological Trace Element Research

, Volume 161, Issue 2, pp 173–179 | Cite as

Effects of Nickel Chloride on the Erythrocytes and Erythrocyte Immune Adherence Function in Broilers

  • Jian Li
  • Bangyuan Wu
  • Hengmin CuiEmail author
  • Xi Peng
  • Jing Fang
  • Zhicai Zuo
  • Junliang Deng
  • Xun Wang
  • Kun Tang
  • Shuang Yin


This study was conducted to investigate the immune adherence function of erythrocytes and erythrocyte induced by dietary nickel chloride (NiCl2) in broilers fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg NiCl2 for 42 days. Blood samples were collected from five broilers in each group at 14, 28, and 42 days of age. Changes of erythrocyte parameters showed that total erythrocyte count (TEC), hemoglobin (Hb) contents, and packed cell volume (PCV) were significantly lower (p < 0.05 or p < 0.01) and erythrocyte osmotic fragility (EOF) was higher (p < 0.05 or p < 0.01) in the 600 and 900 mg/kg groups at 28 and 42 days of age than those in the control group, and the sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) and calcium adenosine triphosphatase (Ca2+-ATPase) activities were significantly decreased (p < 0.05 or p < 0.01) in the NiCl2-treated groups. The results of erythrocyte immune adherence function indicated that erythrocyte C3b receptor rosette rate (E-C3bRR) was significantly decreased (p < 0.05 or p < 0.01) in the 600 and 900 mg/kg groups and in the 300 mg/kg group at 42 days of age, whereas the erythrocyte immune complex rosette rate (E-ICRR) was markedly increased (p < 0.05 or p < 0.01) in the 300, 600, and 900 mg/kg groups at 28 and 42 days of age. It was concluded that dietary NiCl2 in excess of 300 mg/kg caused anemia and impaired the erythrocytic integrity, erythrocytic ability to transport oxygen, and erythrocyte immune adherence function in broilers. Impairment of the erythrocytes and erythrocyte immune adherence function was one of main effect mechanisms of NiCl2 on the blood function.


NiCl2 Na+/K+-ATPase Ca2+-ATPase Erythrocyte Erythrocyte immune adherence function Broiler 



This research was supported by the program for Changjiang scholars and the University Innovative Research Team (IRT 0848), and the Shuangzhi project of Sichuan Agricultural University (03570327)

Conflict of Interest

The authors declare no conflict of interest.


  1. 1.
    Phipps T, Tank SL, Wirtz J, Brewer L, Coyner A, Ortego LS, Fairbrother A (2002) Essentiality of nickel and homeostatic mechanisms for its regulation in terrestrial organisms. Environ Rev 10(4):209–261CrossRefGoogle Scholar
  2. 2.
    Anke M, Grun M, Ditrich G, Groppel B, Hennig A (1974) Low nickel rations for growth and reproduction in pigs. In: Hoekstra WC, Suttle JW, Canther HE, Mertz W (eds) Trace element metabolism in animals 2. University Park Press, BaltimoreGoogle Scholar
  3. 3.
    Nielsen FH, Myron DR, Givand SH, Zimmerman TJ, Ollerich DA (1975) Nickel deficiency in rats. J Nutr 105(12):1620–1630PubMedGoogle Scholar
  4. 4.
    Afridi HI, Kazi TG, Kazi N, Kandhro GA, Baig JA, Shah AQ, Arain MB (2011) Evaluation of status of cadmium, lead, and nickel levels in biological samples of normal and night blindness children of age groups 3–7 and 8–12 years. Biol Trace Elem Res 142(3):350–361PubMedCrossRefGoogle Scholar
  5. 5.
    Stangl GI, Kirchgessner M (1996) Nickel deficiency alters liver lipid metabolism in rats. J Nutr 126(10):2466–2473PubMedGoogle Scholar
  6. 6.
    Nielsen FH, Uthus EO, Poellot RA (1993) Dietary vitamin B12, sulfur amino acids, and odd-chain fatty acids affect the response of rats to nickel deprivation. Biol Trace Elem Res 37(1):1–15PubMedCrossRefGoogle Scholar
  7. 7.
    Uthus EO, Poellot RA (1997) Dietary nickel and folic acid interact to affect folate and methionine metabolism in the rat. Biol Trace Elem Res 58(1–2):25–33PubMedCrossRefGoogle Scholar
  8. 8.
    Ray JR, William J, Douglas S, Ng L (1972) Cobalt (II) and nickel (II) complexes of phosphoglucomutase. Biochemistry 11(15):2800–2804PubMedCrossRefGoogle Scholar
  9. 9.
    Jolly PW (2012) The organic chemistry of nickel: organonickel complexes. Elsevier, New YorkGoogle Scholar
  10. 10.
    Dixon NE, Gazzola C, Blakeley RL, Zerner B (1976) Metal ions in enzymes using ammonia or amides. Science 191(4232):1144–1150PubMedCrossRefGoogle Scholar
  11. 11.
    Fishbein WN, Smith M, Nagarajan K, Sarzi W (1976) The first natural nickel metalloenzyme urease. Fed Proc 55:1680Google Scholar
  12. 12.
    Polacco JC (1977) Nitrogen metabolism in soybean tissue culture II: urea utilization and urease synthesis require Ni2+. Plant Physiol 59(5):827–830PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Diekert G, Thauer RK (1980) The effect of nickel on carbon monoxide dehydrogenase formation in Clostridium thermoaceticum and Clostridium formicoaceticum. FEMS Microbiol Lett 7(3):187–189CrossRefGoogle Scholar
  14. 14.
    Diekert G, Weber B, Thauer RK (1980) Nickel dependence of factor F430 content in Methanobacterium thermoautotrophicum. Arch Microbiol 127(3):273–277CrossRefGoogle Scholar
  15. 15.
    Drake HL, Hu SI, Wood HG (1980) Purification of carbon monoxide dehydrogenase: a nickel enzyme from Clostridium thermocaceticum. J Biol Chem 255(15):7174–7180PubMedGoogle Scholar
  16. 16.
    International Agency for Research on Cancer, IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2001) IARC monographs on the evaluation of carcinogenic risks to humans, vol 78. International Agency for Research on Cancer, LyonGoogle Scholar
  17. 17.
    Kasprzak KS (1991) The role of oxidative damage in metal carcinogenicity. Chem Res Toxicol 4(6):604–615PubMedCrossRefGoogle Scholar
  18. 18.
    Nielsen FH, Myron DR, Givand SH, Ollerich DA (1975) Nickel deficiency and nickel-rhodium interaction in chicks. J Nutr 105(12):1607–1619PubMedGoogle Scholar
  19. 19.
    Wu BY, Cui HM, Peng X, Fang J, Zuo ZC, Deng JL, Huang JY (2013) Dietary nickel chloride induces oxidative intestinal damage in broilers. Int J Environ Res Public Health 10(6):2109–2119PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Wu BY, Cui HM, Peng X, Fang J, Zuo ZC, Deng JL, Huang JY (2013) Investigation of the serum oxidative stress in broilers fed on diets supplemented with nickel chloride. Health 5(3):454–459CrossRefGoogle Scholar
  21. 21.
    Wu BY, Cui HM, Peng X, Fang J, Zuo ZC, Deng JL, Huang JY (2013) Dietary nickel chloride restrains the development of small intestine in broilers. Biol Trace Elem Res 155(2):236–246PubMedCrossRefGoogle Scholar
  22. 22.
    Huang JY, Cui HM, Peng X, Fang J, Zuo ZC, Deng JL, Wang X, Wu BY (2013) The association between splenocyte apoptosis and alterations of Bax, Bcl-2 and caspase-3 mRNA expression, and oxidative stress induced by dietary nickel chloride in broilers. Int J Environ Res Public Health 10(12):7310–7326PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Huang JY, Cui HM, Peng X, Fang J, Zuo ZC, Deng JL, Wang X, Wu BY (2014) Effect of dietary nickel chloride on splenic immune function in broilers. Biol Trace Elem Res 159:183–191PubMedCrossRefGoogle Scholar
  24. 24.
    Fraisl P, Mazzone M, Schmidt T, Carmeliet P (2009) Regulation of angiogenesis by oxygen and metabolism. Dev Cell 16(2):167–179PubMedCrossRefGoogle Scholar
  25. 25.
    Nielsen FH (1980) Effect of form of iron on the interaction between nickel and iron in rats: growth and blood parameters. J Nutr 110(5):965–973PubMedGoogle Scholar
  26. 26.
    Nelson RA (1956) The immune-adherence phenomenon: a hypothetical role of erythrocytes in defence against bacteria and viruses. Proc R Soc Med 49(1):55PubMedPubMedCentralGoogle Scholar
  27. 27.
    Siegel I, Liu TL, Gleicher N (1981) The red-cell immune system. Lancet 318(8246):556–559CrossRefGoogle Scholar
  28. 28.
    Einagel ML, Taylor RP (2000) Transfer of immune complexes from erythrocyte CR1 to mouse macrophages. J Immunol 164(4):1977–1985CrossRefGoogle Scholar
  29. 29.
    Glennon JD, Bibudhendra S (1982) Nickel (II) transport in human blood serum. Studies of nickel (II) binding to human albumin and to native-sequence peptide, and ternary-complex formation with histidine. Biochem J 203:15–23PubMedPubMedCentralGoogle Scholar
  30. 30.
    Jasmin G, Solymoss B (1975) Polycythemia induced in rats by intrarenal injection of nickel sulfide Ni3S2. Exp Biol Med 148(3):774–776CrossRefGoogle Scholar
  31. 31.
    Tkeshelashvili LK, Tsakadze KJ, Khulusauri OV (1989) Effect of some nickel compounds on red blood cell characteristics. Biol Trace Elem Res 21(1):337–342PubMedCrossRefGoogle Scholar
  32. 32.
    Parthipan P, Muniyan M (2013) Effect of heavy metal nickel on hematological parameters of fresh water fish, Cirrhinus mrigala. J Environ Curr Life Sci 1:46–55Google Scholar
  33. 33.
    Demir TA, Akar T, Akyuz F, Isikli B, Kanbak G (2005) Nickel and cadmium concentrations in plasma and Na+/K + ATPase activities in erythrocyte membranes of the people exposed to cement dust emissions. Environ Monit Assess 104(1–3):437–444PubMedCrossRefGoogle Scholar
  34. 34.
    World Health Organization (WHO) (1991) Lindane. Environmental Health Criteria 124. World Health Organization, GenevaGoogle Scholar
  35. 35.
    Tikare SN, Yendigeri S, Gupta AD, Dhundasi SA, Das KK (2012) Effect of garlic (Allium sativum) on hematology and erythrocyte antioxidant defense system of albino rats exposed to heavy metals (nickel II & chromium VI). Indian J Physiol Pharmacol 56(2):137–146PubMedGoogle Scholar
  36. 36.
    Spears JW, Jones EE, Samstrong LJSAD (1984) Effect of dietary nickel on growth, urease activity, blood parameters and tissue mineral concentrations in the Neonatal Pig1-2-3. J Nutr 114:845–853PubMedGoogle Scholar
  37. 37.
    Deluca G, Gugliotta T, Parisi G, Romano P, Geraci A, Romano O, Romano L (2007) Effects of nickel on human and fish red blood cells. Biosci Rep 27(4–5):265–273Google Scholar
  38. 38.
    National Research Council (NRC) (1994) Nutrient requirements of poultry, 9th edn. National Academy Press, Washington, DCGoogle Scholar
  39. 39.
    Ma HD (2004) Physiology experimental course. Sichuan Science and Technology Press, ChengduGoogle Scholar
  40. 40.
    Guo F, Qian BH, Zhang LZ (2002) Modern red blood cell immunology. Second Military Medical University Press, ShanghaiGoogle Scholar
  41. 41.
    Joshi PK, Bose M, Harish D (2002) Haematological changes in the blood of Clarias batrachusn exposed to mercuric chloride. Ecotoxicol Environ Monit 12(2):119–122Google Scholar
  42. 42.
    Wintrobe MM (1974) Clinical hematology, 7th edn. Lea & Febiger, PhiladelphiaGoogle Scholar
  43. 43.
    Clark VL, Kruse JA (1990) Clinical methods: the history, physical, and laboratory examinations. JAMA 264(21):2808–2809CrossRefGoogle Scholar
  44. 44.
    Tennant B, Harrold D, Reina-Guerra M, Kendrick JW, Laben RC (1974) Hematology of the neonatal calf: erythrocyte and leukocyte values of normal calves. Cornell Vet 64(4):516–532PubMedGoogle Scholar
  45. 45.
    Musa SO, Omoregie E (1999) Haematological changes in the mudfish, Clarias gariepinus (Burchell) exposed to malachite green. J Aquat Sci 14(1):37–42Google Scholar
  46. 46.
    Vaseem H, Banerjee TK (2012) Toxicity analysis of effluent released during recovery of metals from polymetallic sea nodules using fish haematological parameters. The functioning of ecosystem. In Tech, Croatia 249–260Google Scholar
  47. 47.
    Kolanjiappan K, Manoharan S, Kayalvizhi M (2002) Measurement of erythrocyte lipids, lipid peroxidation, antioxidants and osmotic fragility in cervical cancer patients. Clin Chim Acta 326(1):143–149PubMedCrossRefGoogle Scholar
  48. 48.
    O’Dell BL, Browning JD, Reeves PG (1987) Zinc deficiency increases the osmotic fragility of rat erythrocytes. J Nutr 117(11):1883–1889PubMedGoogle Scholar
  49. 49.
    Weed RI, Bowdler AJ (1966) Metabolic dependence of the critical hemolytic volume of human erythrocytes: relationship to osmotic fragility and autohemolysis in hereditary spherocytosis and normal red cells. J Clin Invest 45(7):1137–1149PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Kim J, Borges WH, Holliday MA (1962) Correlation between RBC osmotic fragility and serum sodium. Am J Dis Child 104(3):281–288PubMedGoogle Scholar
  51. 51.
    Adenkola AY, Ayo JO (2009) Effect of road transportation on erythrocyte osmotic fragility of pigs administered ascorbic acid during the harmattan season in Zaria, Nigeria. J Cell Anim Biol 3(1):4–8Google Scholar
  52. 52.
    Brzezińska-Slebodzińska E (2001) Erythrocyte osmotic fragility test as the measure of defence against free radicals in rabbits of different age. Acta Vet Hung 49(4):413–419Google Scholar
  53. 53.
    Jadhav SH, Sarkar SN, Aggarwal M, Tripathi HC (2007) Induction of oxidative stress in erythrocytes of male rats subchronically exposed to a mixture of eight metals found as groundwater contaminants in different parts of India. Arch Environ Contam Toxicol 52(1):145–151PubMedCrossRefGoogle Scholar
  54. 54.
    Das KK, Buchner V (2007) Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid. Rev Environ Health 22(2):157–173PubMedCrossRefGoogle Scholar
  55. 55.
    Vijayavel K, Gopalakrishnan S, Balasubramanian MP (2007) Sublethal effect of silver and chromium in the green mussel Perna viridis with reference to alterations in oxygen uptake, filtration rate and membrane bound ATPase system as biomarkers. Chemosphere 69(6):979–986PubMedCrossRefGoogle Scholar
  56. 56.
    Yang YN (1991) The effects of lead on calmodulin, Ca2+-ATPase activity and electron microscopic cytochemical parameters in rats. J Health Toxicol 5(3):160–162Google Scholar
  57. 57.
    Mudad R, Telen MJ (1996) Biologic functions of blood group antigens. Curr Opin Hematol 3(6):473–479PubMedCrossRefGoogle Scholar
  58. 58.
    Zhu YZ, Liu DW, Liu ZY, Li YF (2013) Impact of aluminum exposure on the immune system: a mini review. Environ Toxicol Pharmacol 35(1):82–87PubMedCrossRefGoogle Scholar
  59. 59.
    Zhu YZ, Zhao HS, Li XW, Zhang LC, Hu CW, Bah HSA, Li YF, Zhang ZG (2011) Effects of subchronic aluminum exposure on the immune function of erythrocytes in rats. Biol Trace Elem Res 143(3):1576–1580PubMedCrossRefGoogle Scholar
  60. 60.
    Irmingham DJ, Hebert L (2001) CR1 and CRl-like: the primate immune adherence receptors. Immunol Rev 180(1):100–111CrossRefGoogle Scholar
  61. 61.
    Udin S, Libyh MT, Goossens D, Dervillez X, Philbert F, Reveil B, Bougy F, Tabary T, Rouger P, Klatzmann D, Cohen JHM (2000) A soluble recombinant multimeric anti-RH (D) single-chain Fv/CR1 molecule restores the immune complex binding ability of CR1-deficient erythrocytes. J Immunol 164(3):1505–1513CrossRefGoogle Scholar
  62. 62.
    Jiang JB, Wu CH, Gao H, Song GD, Li HQ (2010) Effects of astragalus polysaccharides on immunologic function of erythrocyte in chickens infected with infectious bursa disease virus. Vaccine 28(34):5614–5616PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jian Li
    • 1
  • Bangyuan Wu
    • 1
  • Hengmin Cui
    • 1
    • 2
    Email author
  • Xi Peng
    • 1
    • 2
  • Jing Fang
    • 1
    • 2
  • Zhicai Zuo
    • 1
    • 2
  • Junliang Deng
    • 1
    • 2
  • Xun Wang
    • 1
    • 2
  • Kun Tang
    • 1
  • Shuang Yin
    • 1
  1. 1.Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan ProvinceSichuan Agricultural UniversityYa’anChina
  2. 2.College of Veterinary MedicineSichuan Agricultural UniversityYa’anChina

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