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Elemental imbalance elicited by arsenic and copper exposures leads to oxidative stress and immunotoxicity in chicken gizzard, activating the protective effects of heat shock proteins

  • Menghao Guo
  • Hongjing Zhao
  • Yu Wang
  • Juanjuan Liu
  • Dongxue Fei
  • Xin Yang
  • Mengyao Mu
  • Mingwei XingEmail author
Research Article
  • 86 Downloads

Abstract

Arsenic (As) and copper (Cu) are ubiquitous pollutants that pose a threat to the environment. Our aim is to study the underlying mechanisms by which As and Cu act on the chicken gizzard. In order to detect ionic disorders in chicken gizzard under chronic treatment with As3+ and/or Cu2+ and whether they can induce oxidative damage as well as immune disorders, 30 mg/kg arsenic trioxide (As2O3) and/or 300 mg/kg copper sulfate (CuSO4) were added to the chicken’s basal diet. After 12 weeks of exposure, trace elements were found to have significant interference, accompanied by damage to the antioxidant system. In addition, As3+ and/or Cu2+ activated the nuclear factor kappa B (NF-κB), inducing severe inflammation. At the same time, damaged structural integrity which might be caused by inflammation was discovered after hematoxylin and eosin (H&E) staining. Moreover, symbolic Th1/Th2 (Th, helper T cell) drift was also observed in treatment groups, meaning that immune function is left to be affected, and the increment in heat shock proteins may be a self-protective mechanism of gizzard. Interestingly, we found that the damage to the gizzard of chicken was aggravated in a time-dependent manner, and the combined exposure was more pathogenic than the single exposure, of which the mechanism needs further exploration. Together, this work helps move us toward a better understanding of the molecular mechanisms that mediate the interactions between Cu excess and As3+ exposures and possible health consequences in susceptible species.

Keywords

Arsenic Copper Oxidative stress Inflammation Immune disorders Heat shock proteins 

Notes

Funding information

This research was supported by the National Key Research and Development Program of China (Grant No. 2017YFD0501702); the National Natural Science Foundation of China (Grant No. 31672619) and the Fundamental Research Funds for the Central Universities (Grant No. 2572016EAJ5).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11356_2019_6702_MOESM1_ESM.doc (72 kb)
ESM 1 (DOC 72 kb)

References

  1. Alexander TC, Han FX, Arslan Z, Tchounwou PB (2019) Toxicity of As in Crassostrea virginica (Gmelin, 1791) from the Northern Gulf of Mexico at the presence of Zn and its antioxidant defense mechanisms. Ecotoxicol Environ Saf 172:514–522CrossRefGoogle Scholar
  2. Baker RG, Hayden MS, Ghosh S (2011) NF-kappaB, inflammation, and metabolic disease. Cell Metab 13:11–22CrossRefGoogle Scholar
  3. Brahman KD, Kazi TG, Afridi HI, Baig JA, Arain SS, Talpur FN, Kazi AG, Ali J, Panhwar AH, Arain MB (2016) Exposure of children to arsenic in drinking water in the Tharparkar region of Sindh, Pakistan. Sci Total Environ 544:653–660CrossRefGoogle Scholar
  4. Chen M, Li X, Fan R, Yang J, Jin X, Hamid S, Xu S (2018) Cadmium induces BNIP3-dependent autophagy in chicken spleen by modulating miR-33-AMPK axis. Chemosphere 194:396–402CrossRefGoogle Scholar
  5. Chen M, Li X, Shi Q, Zhang Z, Xu S (2019a) Hydrogen sulfide exposure triggers chicken trachea inflammatory injury through oxidative stress-mediated FOS/IL8 signaling. J Hazard Mater 368:243–254CrossRefGoogle Scholar
  6. Chen J, Xu Y, Han Q, Yao Y, Xing H, Teng X (2019b) Immunosuppression, oxidative stress, and glycometabolism disorder caused by cadmium in common carp (Cyprinus carpio L.): Application of transcriptome analysis in risk assessment of environmental contaminant cadmium. J Hazard Mater 366:386–394CrossRefGoogle Scholar
  7. Cui X, Okayasu R (2008) Arsenic accumulation, elimination, and interaction with copper, zinc and manganese in liver and kidney of rats. Food Chem Toxicol 46:3646–3650CrossRefGoogle Scholar
  8. Fernandez CP, Afrin F, Flores RA, Kim WH, Jeong J, Kim S, Lillehoj HS, Min W (2018) Identification of duck IL-4 and its inhibitory effect on IL-17A expression in R. anatipestifer-stimulated splenic lymphocytes. Mol Immunol 95:20–29CrossRefGoogle Scholar
  9. Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51:257–281CrossRefGoogle Scholar
  10. Freedman JH, Ciriolo MR, Peisach J (1989) The role of glutathione in copper metabolism and toxicity. J Biol Chem 264:5598–5605Google Scholar
  11. Gong ZG, Wang XY, Wang JH, Fan RF, Wang L (2019) Trehalose prevents cadmium-induced hepatotoxicity by blocking Nrf2 pathway, restoring autophagy and inhibiting apoptosis. J Inorg Biochem 192:62–71CrossRefGoogle Scholar
  12. Gousios AG, Adelson L (1959) Electrocardiographic and radiographic findings in acute arsenic poisoning. Am J Med 27:659–663CrossRefGoogle Scholar
  13. Guo Y, Zhao P, Guo G, Hu Z, Tian L, Zhang K, Zhang W, Xing M (2015) The role of oxidative stress in gastrointestinal tract tissues induced by arsenic toxicity in cocks. Biol Trace Elem Res 168:490–499CrossRefGoogle Scholar
  14. Hang K, Ye C, Chen E, Zhang W, Xue D, Pan Z (2018) Role of the heat shock protein family in bone metabolism. Cell Stress Chaperones 23:1153–1164CrossRefGoogle Scholar
  15. Hodge DR, Hurt EM, Farrar WL (2005) The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer 41:2502–2512CrossRefGoogle Scholar
  16. Hu X, Chi Q, Wang D, Chi X, Teng X, Li S (2018) Hydrogen sulfide inhalation-induced immune damage is involved in oxidative stress, inflammation, apoptosis and the Th1/Th2 imbalance in broiler bursa of Fabricius. Ecotoxicol Environ Saf 164:201–209CrossRefGoogle Scholar
  17. Jacquier-Sarlin MR, Fuller K, Dinh-Xuan AT, Richard MJ, Polla BS (1994) Protective effects of hsp70 in inflammation. Experientia 50:1031–1038CrossRefGoogle Scholar
  18. Jin X, Xu Z, Zhao X, Chen M, Xu S (2017) The antagonistic effect of selenium on lead-induced apoptosis via mitochondrial dynamics pathway in the chicken kidney. Chemosphere 180:259–266CrossRefGoogle Scholar
  19. Jung YJ, Isaacs JS, Lee S, Trepel J, Neckers L (2003) IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB J 17:2115–2117CrossRefGoogle Scholar
  20. Li SW, Shao YZ, Zhao HJ, Wang Y, Li JL, Xing MW (2017) Analysis of 28 trace elements in the blood and serum antioxidant status in chickens under arsenic and/or copper exposure. Environ Sci Pollut Res Int 24:27303–27313CrossRefGoogle Scholar
  21. Liu SX, Davidson MM, Tang X, Walker WF, Athar M, Ivanov V, Hei TK (2005) Mitochondrial damage mediates genotoxicity of arsenic in mammalian cells. Cancer Res 65:3236–3242CrossRefGoogle Scholar
  22. Liu G, Wang ZK, Wang ZY, Yang DB, Liu ZP, Wang L (2016) Mitochondrial permeability transition and its regulatory components are implicated in apoptosis of primary cultures of rat proximal tubular cells exposed to lead. Arch Toxicol 90:1193–1209CrossRefGoogle Scholar
  23. Liu J, Zhao H, Wang Y, Shao Y, Li J, Xing M (2018) Alterations of antioxidant indexes and inflammatory cytokine expression aggravated hepatocellular apoptosis through mitochondrial and death receptor-dependent pathways in Gallus gallus exposed to arsenic and copper. Environ Sci Pollut Res Int 25:15462–15473CrossRefGoogle Scholar
  24. McNulty M, Puljung M, Jefford G, Dubreuil RR (2001) Evidence that a copper-metallothionein complex is responsible for fluorescence in acid-secreting cells of the Drosophila stomach. Cell Tissue Res 304:383–389CrossRefGoogle Scholar
  25. Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, Suk WA (2013) The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem. Environ Health Perspect 121:295–302CrossRefGoogle Scholar
  26. Ng JC, Wang J, Shraim A (2003) A global health problem caused by arsenic from natural sources. Chemosphere 52:1353–1359CrossRefGoogle Scholar
  27. Ozcelik D, Ozaras R, Gurel Z, Uzun H, Aydin S (2003) Copper-mediated oxidative stress in rat liver. Biol Trace Elem Res 96:209–215CrossRefGoogle Scholar
  28. Quintana FJ, Cohen IR (2011) The HSP60 immune system network. Trends Immunol 32:89–95CrossRefGoogle Scholar
  29. Rana T, Bera AK, Mondal DK, Das S, Bhattacharya D, Samanta S, Pan D, Das SK (2014) Arsenic residue in the products and by-products of chicken and ducks: a possible concern of avian health and environmental hazard to the population in West Bengal, India. Toxicol Ind Health 30:576–580CrossRefGoogle Scholar
  30. Rodriguez-Arambula A, Torres-Alvarez B, Cortes-Garcia D, Fuentes-Ahumada C, Castanedo-Cazares JP (2015) CD4, IL-17, and COX-2 are associated with subclinical inflammation in malar melasma. Am J Dermatopathol 37:761–766CrossRefGoogle Scholar
  31. Sanchez W, Palluel O, Meunier L, Coquery M, Porcher JM, Ait-Aissa S (2005) Copper-induced oxidative stress in three-spined stickleback: relationship with hepatic metal levels. Environ Toxicol Pharmacol 19:177–183CrossRefGoogle Scholar
  32. Schmolke G, Elsenhans B, Ehtechami C, Forth W (1992) Arsenic-copper interaction in the kidney of the rat. Hum Exp Toxicol 11:315–321CrossRefGoogle Scholar
  33. Shao Y, Zhao H, Wang Y, Liu J, Li J, Chai H, Xing M (2018) Arsenic and/or copper caused inflammatory response via activation of inducible nitric oxide synthase pathway and triggered heat shock protein responses in testis tissues of chicken. Environ Sci Pollut Res 25:7719–7729CrossRefGoogle Scholar
  34. Sun Z, Xu Z, Wang D, Yao H, Li S (2018) Selenium deficiency inhibits differentiation and immune function and imbalances the Th1/Th2 of dendritic cells. Metallomics 10:759–767CrossRefGoogle Scholar
  35. Swaroop S, Mahadevan A, Shankar SK, Adlakha YK, Basu A (2018) HSP60 critically regulates endogenous IL-1beta production in activated microglia by stimulating NLRP3 inflammasome pathway. J Neuroinflammation 15:177CrossRefGoogle Scholar
  36. Wang W, Chen M, Jin X, Li X, Yang Z, Lin H, Xu S (2018a) H2S induces Th1/Th2 imbalance with triggered NF-kappaB pathway to exacerbate LPS-induce chicken pneumonia response. Chemosphere 208:241–246CrossRefGoogle Scholar
  37. Wang Y, Jiang L, He J, Hu M, Zeng F, Li Y, Tian H, Luo X (2018b) The adverse effects of Se toxicity on inflammatory and immune responses in chicken spleens. Biol Trace Elem Res 185:170–176CrossRefGoogle Scholar
  38. Wang Y, Zhao H, Guo M, Shao Y, Liu J, Jiang G, Xing M (2018c) Arsenite renal apoptotic effects in chickens co-aggravated by oxidative stress and inflammatory response. Metallomics 10:1805–1813CrossRefGoogle Scholar
  39. Wang Y, Zhao H, Liu J, Shao Y, Li J, Luo L, Xing M (2018d) Copper and arsenic-induced oxidative stress and immune imbalance are associated with activation of heat shock proteins in chicken intestines. Int Immunopharmacol 60:64–75CrossRefGoogle Scholar
  40. Wang Y, Zhao H, Shao Y, Liu J, Li J, Xing M (2018e) Interplay between elemental imbalance-related PI3K/Akt/mTOR-regulated apoptosis and autophagy in arsenic (III)-induced jejunum toxicity of chicken. Environ Sci Pollut Res Int 25:18662–18672CrossRefGoogle Scholar
  41. Wang Y, Zhao H, Shao Y, Liu J, Li J, Luo L, Xing M (2018f) Copper (II) and/or arsenite-induced oxidative stress cascades apoptosis and autophagy in the skeletal muscles of chicken. Chemosphere 206:597–605CrossRefGoogle Scholar
  42. Wang Y, Zhao H, Shao Y, Liu J, Li J, Luo L, Xing M (2018g) Copper or/and arsenic induces autophagy by oxidative stress-related PI3K/AKT/mTOR pathways and cascaded mitochondrial fission in chicken skeletal muscle. J Inorg Biochem 188:1–8CrossRefGoogle Scholar
  43. Wang LY, Fan RF, Yang DB, Zhang D, Wang L (2019a) Puerarin reverses cadmium-induced lysosomal dysfunction in primary rat proximal tubular cells via inhibiting Nrf2 pathway. Biochem Pharmacol 162:132–141CrossRefGoogle Scholar
  44. Wang Y, Zhao H, Fei D, Shao Y, Liu J, Jiang G, Xing M (2019b) Discrepant effects of copper (II) stress on different types of skeletal muscles in chicken: elements and amino acids. Ecotox Environ Safe 167:227–235CrossRefGoogle Scholar
  45. Wang Y, Zhao H, Guo M, Fei D, Zhang L, Xing M (2019c) Targeting the miR-122/PKM2 autophagy axis relieves arsenic stress. J Hazard Mater.  https://doi.org/10.1016/j.jhazmat.2019.121217 CrossRefGoogle Scholar
  46. Xing M, Jin X, Wang J, Shi Q, Cai J, Xu S (2018) The antagonistic effect of selenium on lead-induced immune dysfunction via recovery of cytokine and heat shock protein expression in chicken neutrophils. Biol Trace Elem Res 185:162–169CrossRefGoogle Scholar
  47. Yim MB, Chock PB, Stadtman ER (1993) Enzyme function of copper, zinc superoxide dismutase as a free radical generator. J Biol Chem 268:4099–4105Google Scholar
  48. Zhang Z, Liu Q, Cai J, Yang J, Shen Q, Xu S (2017a) Chlorpyrifos exposure in common carp (Cyprinus carpio L.) leads to oxidative stress and immune responses. Fish Shellfish Immunol 67:604–611CrossRefGoogle Scholar
  49. Zhang Z, Zheng Z, Cai J, Liu Q, Yang J, Gong Y, Wu M, Shen Q, Xu S (2017b) Effect of cadmium on oxidative stress and immune function of common carp (Cyprinus carpio L.) by transcriptome analysis. Aquat Toxicol 192:171–177CrossRefGoogle Scholar
  50. Zhao P, Zhang K, Guo G, Sun X, Chai H, Zhang W, Xing M (2016) Heat shock protein alteration in the gastrointestinal tract tissues of chickens exposed to arsenic trioxide. Biol Trace Elem Res 170:224–236CrossRefGoogle Scholar
  51. Zhao H, Wang Y, Shao Y, Liu J, Liu Y, Xing M (2018a) Deciphering the ionic homeostasis, oxidative stress, apoptosis, and autophagy in chicken intestine under copper(II) stress. Environ Sci Pollut Res Int 25:33172–33182CrossRefGoogle Scholar
  52. Zhao H, Wang Y, Shao Y, Liu J, Wang S, Xing M (2018b) Oxidative stress-induced skeletal muscle injury involves in NF-kappaB/p53-activated immunosuppression and apoptosis response in copper (II) or/and arsenite-exposed chicken. Chemosphere 210:76–84CrossRefGoogle Scholar
  53. Zhao H, Wang Y, Liu J, Guo M, Fei D, Yu H, Xing M (2019) The cardiotoxicity of the common carp (Cyprinus carpio) exposed to environmentally relevant concentrations of arsenic and subsequently relieved by zinc supplementation. Environ Pollut 253:741–748CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Menghao Guo
    • 1
  • Hongjing Zhao
    • 1
  • Yu Wang
    • 1
  • Juanjuan Liu
    • 1
  • Dongxue Fei
    • 1
  • Xin Yang
    • 1
  • Mengyao Mu
    • 1
  • Mingwei Xing
    • 1
    Email author
  1. 1.College of Wildlife and Protected AreaNortheast Forestry UniversityHarbinPeople’s Republic of China

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