Skip to main content
Log in

NiCl2-Down-Regulated Antioxidant Enzyme mRNA Expression Causes Oxidative Damage in the Broilers Kidney

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

Abstract

The kidney serves as a major organ of nickel (Ni) excretion and is a target organ for acute Ni toxicity due to Ni accumulation. There are no studies on the Ni or Ni compound-regulated antioxidant enzyme mRNA expression in animals and human beings at present. This study was conducted to investigate the pathway of nickel chloride (NiCl2)-caused renal oxidative damage by the methods of biochemistry, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Two hundred and eighty one-day-old broilers were randomly divided into four groups and fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg of NiCl2 for 42 days. Dietary NiCl2 elevated the malondialdehyde (MDA), nitric oxide (NO), 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents, and reduced the ability to inhibit hydroxy radical in the NiCl2-treated groups. Also, the renal inducible nitric oxide synthase (iNOS) activity and mRNA expression levels were increased. The total antioxidant (T-AOC) and activities of antioxidant enzymes including copper zinc superoxide dismutase (CuZn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glutathione-s-transferase (GST) were decreased, and the glutathione (GSH) contents as well were decreased in the kidney. Concurrently, the renal CuZn-SOD, Mn-SOD, CAT, GSH-Px, GST, and GR mRNA expression levels were decreased. The above-mentioned results showed that dietary NiCl2 in excess of 300 mg/kg caused renal oxidative damage by reducing mRNA expression levels and activities of antioxidant enzymes, and then enhancing free radicals generation, lipid peroxidation, and DNA oxidation.

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

Similar content being viewed by others

References

  1. Chau Y, Kulikovsky-Cordeiro O (1995) Occurrence of nickel in the Canadian environment. Environ Rev 3(1):95–120. doi:10.1139/a95-004

    Article  CAS  Google Scholar 

  2. Pasanen K, Pukkala E, Turunen AW, Patama T, Jussila I, Makkonen S et al (2012) Mortality among population with exposure to industrial air pollution containing nickel and other toxic metals. J Occup Environ Med 54(5):583–591

    Article  CAS  PubMed  Google Scholar 

  3. Henderson RG, Durando J, Oller AR, Merkel DJ, Marone PA, Bates HK (2012) Acute oral toxicity of nickel compounds. Regul Toxicol Pharm 62(3):425–432. doi:10.1016/j.yrtph.2012.02.002

    Article  CAS  Google Scholar 

  4. Ragsdale SW (1998) Nickel biochemistry. Curr Opin Chem Biol 2(2):208–215. doi:10.1016/S1367-5931(98)80062-8

    Article  CAS  PubMed  Google Scholar 

  5. Denkhausa ESK (2002) Nickel essentiality, toxicity, and carcinogenicity. Crit Rev Oncol Hemat 42(1):35–36. doi:10.1016/S1040-8428(01)00214-1

    Article  Google Scholar 

  6. Das KK, Das SN, Dhundasi SA (2008) Nickel, its adverse health effects & oxidative stress. Indian J Med Res 128(4):412–425

    CAS  PubMed  Google Scholar 

  7. Cavallo D, Ursini C, Setini A, Chianese C, Piegari P, Perniconi B et al (2003) Evaluation of oxidative damage and inhibition of DNA repair in an in vitro study of nickel exposure. Toxicol In Vitro 17(5):603–607. doi:10.1016/S0887-2333(03)00138-3

    Article  CAS  PubMed  Google Scholar 

  8. Salnikow K, Zhitkovich A (2008) Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol 21(1):28–44. doi:10.1021/tx700198a

    Article  PubMed Central  PubMed  Google Scholar 

  9. Xu Z, Ren T, Xiao C, Li H, Wu T (2011) Nickel promotes the invasive potential of human lung cancer cells via TLR4/MyD88 signaling. Toxicology 285(1–2):25–30. doi:10.1016/j.tox.2011.03.016

    Article  CAS  PubMed  Google Scholar 

  10. Chen J, Han J, Wang J (2013) Prevention of cytotoxicity of nickel by quercetin: the role of reactive oxygen species and histone acetylation. Toxicol Ind Health 29(4):360–366. doi:10.1177/0748233711433940

    Article  CAS  PubMed  Google Scholar 

  11. Dahdouh F, Raane M, Thevenod F, Lee WK (2014) Nickel-induced cell death and survival pathways in cultured renal proximal tubule cells: roles of reactive oxygen species, ceramide and ABCB1. Arch Toxicol 88(4):881–892. doi:10.1007/s00204-014-1194-x

    Article  CAS  PubMed  Google Scholar 

  12. Liu CM, Zheng GH, Ming QL, Chao C, Sun JM (2013) Sesamin protects mouse liver against nickel-induced oxidative DNA damage and apoptosis by the PI3K-Akt pathway. J Agr Food Chem 61(5):1146–1154. doi:10.1021/jf304562b

    Article  CAS  Google Scholar 

  13. Wang M, Wang G (2010) Oxidative damage effects in the copepod Tigriopus japonicus Mori experimentally exposed to nickel. Ecotoxicology 19(2):273–284. doi:10.1007/s10646-009-0410-6

    Article  CAS  PubMed  Google Scholar 

  14. Wu B, Cui H, Peng X, Fang J, Zuo Z, Deng J et al (2014) Dietary nickel chloride induces oxidative stress, apoptosis and alters Bax/Bcl-2 and caspase-3 mRNA expression in the cecal tonsil of broilers. Food Chem Toxicol 63:18–29. doi:10.1016/j.fct.2013.10.033

    Article  CAS  PubMed  Google Scholar 

  15. Wu B, Cui H, Peng X, Fang J, Zuo Z, Deng J et al (2013) Dietary nickel chloride induces oxidative intestinal damage in broilers. Int J Environ Res Public Health 10(6):2109–2119. doi:10.3390/ijerph10062109

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Huang J, Cui H, Peng X, Fang J, Zuo Z, Deng J et al (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):7310–7326. doi:10.3390/ijerph10127310

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Klaassen CD (2001) Casarett and Doull's toxicology: the basic science of poisons, vol 1236. McGraw-Hill, New York

    Google Scholar 

  18. Tyagi R, Rana P, Gupta M, Khan AR, Bhatnagar D, Bhalla PJ et al (2013) Differential biochemical response of rat kidney towards low and high doses of NiCl2 as revealed by NMR spectroscopy. J Appl Toxicol 33(2):134–141. doi:10.1002/jat.1730

    Article  PubMed  Google Scholar 

  19. Kubrak OI, Husak VV, Rovenko BM, Poigner H, Mazepa MA, Kriews M et al (2012) Tissue specificity in nickel uptake and induction of oxidative stress in kidney and spleen of goldfish Carassius auratus, exposed to waterborne nickel. Aquat Toxicol 118–119:88–96. doi:10.1016/j.aquatox.2012.03.016

    Article  PubMed  Google Scholar 

  20. NRC (1994) Nutrient requirements of poultry. National Research Council. National Academy Press Washington^ eUSA USA

  21. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. doi:10.1016/0003-2697(76)90527-3

    Article  CAS  PubMed  Google Scholar 

  22. Gaca MD, Pickering JA, Arthur MJ, Benyon RC (1999) Human and rat hepatic stellate cells produce stem cell factor: a possible mechanism for mast cell recruitment in liver fibrosis. J Hepatol 30(5):850–858. doi:10.1016/S0168-8278(99)80139-1

    Article  CAS  PubMed  Google Scholar 

  23. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25(4):402–408. doi:10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  24. Rao MV, Chawla SL, Sharma SR (2009) Protective role of vitamin E on nickel and/or chromium induced oxidative stress in the mouse ovary. Food Chem Toxicol 47(6):1368–1371. doi:10.1016/j.fct.2009.03.018

    Article  CAS  PubMed  Google Scholar 

  25. Lou J, Jin L, Wu N, Tan Y, Song Y, Gao M et al (2013) DNA damage and oxidative stress in human B lymphoblastoid cells after combined exposure to hexavalent chromium and nickel compounds. Food Chem Toxicol 55:533–540. doi:10.1016/j.fct.2013.01.053

    Article  CAS  PubMed  Google Scholar 

  26. Kohen R, Nyska A (2002) Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol 30(6):620–650. doi:10.1080/01926230290166724

    Article  CAS  PubMed  Google Scholar 

  27. Chen JJ, Yu BP (1994) Alterations in mitochondrial membrane fluidity by lipid peroxidation products. Free Radical Bio Med 17(5):411–418. doi:10.1016/0891-5849(94)90167-8

    Article  CAS  Google Scholar 

  28. Marnett LJ (1999) Lipid peroxidation-DNA damage by malondialdehyde. Mutat Res 424(1–2):83–95. doi:10.1016/S0027-5107(99)00010-X

    Article  CAS  PubMed  Google Scholar 

  29. Valavanidis A, Vlachogianni T, Fiotakis C (2009) 8-Hydroxy-2' -deoxyguanosine (8-OHdG): a critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Heal C 27(2):120–139. doi:10.1080/10590500902885684

    Article  CAS  Google Scholar 

  30. Burton GJ, Jauniaux E (2011) Oxidative stress. Best Pract Res Clin Ob 25(3):287–299. doi:10.1016/j.bpobgyn.2010.10.016

    Article  Google Scholar 

  31. Klein CB, Frenkel K, Costa M (1991) The role of oxidative processes in metal carcinogenesis. Chem Res Toxicol 4(6):592–604. doi:10.1021/tx00024a001

    Article  CAS  PubMed  Google Scholar 

  32. Knowles RG, Moncada S (1994) Nitric oxide synthases in mammals. Biochem J 298(Pt 2):249–258

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Tian L, Lawrence DA (1996) Metal-induced modulation of nitric oxide production in vitro by murine macrophages: lead, nickel, and cobalt utilize different mechanisms. Toxicol Appl Pharm 141(2):540–547. doi:10.1006/taap.1996.0320

    Article  CAS  Google Scholar 

  34. Goebeler M, Roth J, Bröcker E, Sorg C, Schulze-Osthoff K (1995) Activation of nuclear factor-kappa B and gene expression in human endothelial cells by the common haptens nickel and cobalt. J Immunol 155(5):2459–2467

    CAS  PubMed  Google Scholar 

  35. Kwon HY, Choi SY, Won MH, Kang T-C, Kang JH (2000) Oxidative modification and inactivation of Cu, Zn-superoxide dismutase by 2, 2′-azobis (2-amidinopropane) dihydrochloride. BBA-Protein Struct M 1543(1):69–76. doi:10.1016/s0167-4838(00)00197-7

    Article  CAS  Google Scholar 

  36. Rodriguez RE, Misra M, Kasprzak KS (1990) Effects of nickel on catalase activity in vitro and in vivo. Toxicology 63(1):45–52. doi:10.1016/0300-483x(90)90067-q

    Article  CAS  PubMed  Google Scholar 

  37. Pari L, Amudha K (2011) Hepatoprotective role of naringin on nickel-induced toxicity in male Wistar rats. Eur J Pharmacol 650(1):364–370. doi:10.1016/j.ejphar.2010.09.068

    Article  CAS  PubMed  Google Scholar 

  38. Boadi WY, Harris S, Anderson JB, Adunyah SE (2013) Lipid peroxides and glutathione status in human progenitor mononuclear (U937) cells following exposure to low doses of nickel and copper. Drug Chem Toxicol 36(2):155–162. doi:10.3109/01480545.2012.660947

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Salnikow K, Gao M, Voitkun V, Huang X, Costa M (1994) Altered oxidative stress responses in nickel-resistant mammalian cells. Cancer Res 54(24):6407–6412

    CAS  PubMed  Google Scholar 

  40. Krezel A, Szczepanik W, Sokolowska M, Jezowska-Bojczuk M, Bal W (2003) Correlations between complexation modes and redox activities of Ni(II)-GSH complexes. Chem Res Toxicol 16(7):855–864. doi:10.1021/tx034012k

    Article  CAS  PubMed  Google Scholar 

  41. Cabrini L, Bergami R, Fiorentini D, Marchetti M, Landi L, Tolomelli B (1998) Vitamin B6 deficiency affects antioxidant defences in rat liver and heart. IUBMB Life 46(4):689–697. doi:10.1080/15216549800204222

    Article  CAS  Google Scholar 

  42. Elia AC, Anastasi V, Dörr AJM (2006) Hepatic antioxidant enzymes and total glutathione of Cyprinus carpio exposed to three disinfectants, chlorine dioxide, sodium hypochlorite and peracetic acid, for superficial water potabilization. Chemosphere 64(10):1633–1641

    Article  CAS  PubMed  Google Scholar 

  43. Ran Q, Liang H, Ikeno Y, Qi W, Prolla TA, Roberts LJ et al (2007) Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis. J Gerontol A-Biol 62(9):932–942. doi:10.1093/gerona/62.9.932

    Article  Google Scholar 

  44. Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol 45:51–88. doi:10.1146/annurev.pharmtox.45.120403.095857

    Article  CAS  Google Scholar 

  45. Misra M, Rodriguez RE, Kasprzak KS (1990) Nickel induced lipid peroxidation in the rat: correlation with nickel effect on antioxidant defense systems. Toxicology 64(1):1–17. doi:10.1016/0300-483X(90)90095-X

    Article  CAS  PubMed  Google Scholar 

  46. Aravind P, Prasad MN (2005) Modulation of cadmium-induced oxidative stress in Ceratophyllum demersum by zinc involves ascorbate–glutathione cycle and glutathione metabolism. Plant Physiol Bioch 43(2):107–116. doi:10.1016/j.plaphy.2005.01.002

    Article  CAS  Google Scholar 

  47. Röhrdanz E, Kahl R (1998) Alterations of antioxidant enzyme expression in response to hydrogen peroxide. Free Radical Bio Med 24(1):27–38. doi:10.1016/s0891-5849(97)00159-7

    Article  Google Scholar 

  48. Bermano G, Nicol F, Dyer JA, Sunde RA, Beckett GJ, Arthur JR et al (1995) Tissue-specific regulation of selenoenzyme gene expression during selenium deficiency in rats. Biochem J 311(Pt 2):425–430

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Yarru LP, Settivari RS, Gowda NK, Antoniou E, Ledoux DR, Rottinghaus GE (2009) Effects of turmeric (Curcuma longa) on the expression of hepatic genes associated with biotransformation, antioxidant, and immune systems in broiler chicks fed aflatoxin. Poultry Sci 88(12):2620–2627. doi:10.3382/ps.2009-00204

    Article  CAS  Google Scholar 

Download references

Acknowledgment

The study was supported by the program for Changjiang scholars and innovative research team in university (IRT 0848) and the Shuangzhi project of Sichuan Agricultural University (03570327).

Conflict of Interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hengmin Cui.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, H., Wu, B., Cui, H. et al. NiCl2-Down-Regulated Antioxidant Enzyme mRNA Expression Causes Oxidative Damage in the Broilers Kidney. Biol Trace Elem Res 162, 288–295 (2014). https://doi.org/10.1007/s12011-014-0132-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-0132-3

Keywords

Navigation