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
In this study, we sought to investigate the effects of sub-chronic exposure of arsenic (As) and copper (Cu) on oxidative stress, inflammatory response, and mitochondria and death receptor apoptosis pathways in chicken liver. Seventy-two 1-day-old male Hy-line chickens were treated with basal diet, 30 mg/kg arsenic trioxide (As2O3), or/and 300 mg/kg copper sulfate (CuSO4) for 4, 8, and 12 weeks. Study revealed that exposure to As or/and Cu undermined the antioxidant function and increased lipid peroxidation. Worse yet, liver cell swollen, vacuolar degeneration, and inflammatory cell infiltration were accompanied by an increase of the nuclear factor-κB (NF-κB) and its downstream inflammation-related genes after exposure to As or/and Cu. Furthermore, mitochondria swollen and chromatin condensation were found in As and Cu groups, and hepatocyte nuclear membrane rupture and markedly increased (P < 0.01) apoptosis index were observed in As combined with Cu group. Meanwhile, the transcription and protein expression levels of Bcl-2-associated X protein (Bax), p53, cytochrome c (Cyt c), and caspase-3, 8, 9 were upregulated and B cell lymphoma-2 (Bcl-2) was downregulated in As, Cu, and As + Cu groups in the liver tissues (P < 0.05, P < 0.01). Our results indicated that exposure to As or/and Cu could lead to oxidative stress, inflammatory response, and tissue damage and aggravate hepatocellular apoptosis through mitochondrial and death receptor-dependent pathways in chicken liver. And As and Cu showed a possible synergistic relationship in liver damage.
KeywordsChicken liver Arsenic Copper Oxidative stress Inflammation Apoptosis
Compliance with ethical standards
Animal care and all experimental procedures were done according to the guidelines of the Institutional Animal Care and Use Committee of Northeast Forestry University (approval no. UT-31; June 20, 2014).
Conflict of interest
The authors declare that they have no conflict of interest.
- Altun S, Ozdemir S, Arslan H (2017) Histopathological effects, responses of oxidative stress, inflammation, apoptosis biomarkers and alteration of gene expressions related to apoptosis, oxidative stress, and reproductive system in chlorpyrifos-exposed common carp (Cyprinus carpio L.) Environ Pollut 230:432–443. https://doi.org/10.1016/j.envpol.2017.06.085 CrossRefGoogle Scholar
- Cao H, Gao F, Xia B, Zhang M, Liao Y, Yang Z, Hu G, Zhang C (2016b) Alterations in trace element levels and mRNA expression of Hsps and inflammatory cytokines in livers of duck exposed to molybdenum or/and cadmium. Ecotoxicol Environ Saf 125:93–101. https://doi.org/10.1016/j.ecoenv.2015.12.003 CrossRefGoogle Scholar
- Chi Q, Liu T, Sun Z, Tan S, Li S, Li S (2017) Involvement of mitochondrial pathway in environmental metal pollutant lead-induced apoptosis of chicken liver: perspectives from oxidative stress and energy metabolism. Environ Sci Pollut Res Int 24:28121–28131. https://doi.org/10.1007/s11356-017-0411-6 CrossRefGoogle Scholar
- Choudhury S, Ghosh S, Mukherjee S, Gupta P, Bhattacharya S, Adhikary A, Chattopadhyay S (2016) Pomegranate protects against arsenic-induced p53-dependent ROS-mediated inflammation and apoptosis in liver cells. J Nutr Biochem 38:25–40. https://doi.org/10.1016/j.jnutbio.2016.09.001 CrossRefGoogle Scholar
- Li S, Zhao H, Wang Y, Shao Y, Li J, Liu J, Xing M (2017a) The inflammatory responses in Cu-mediated elemental imbalance is associated with mitochondrial fission and intrinsic apoptosis in Gallus gallus heart. Chemosphere 189:489–497. https://doi.org/10.1016/j.chemosphere.2017.09.099 CrossRefGoogle Scholar
- Li X, Xing M, Chen M, Zhao J, Fan R, Zhao X, Cao C, Yang J, Zhang Z, Xu S (2017c) Effects of selenium-lead interaction on the gene expression of inflammatory factors and selenoproteins in chicken neutrophils. Ecotoxicol Environ Saf 139:447–453. https://doi.org/10.1016/j.ecoenv.2017.02.017 CrossRefGoogle Scholar
- 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 90:1193–1209. https://doi.org/10.1007/s00204-015-1547-0 CrossRefGoogle Scholar
- Lu J, Wu DM, Zheng YL, Sun DX, Hu B, Shan Q, Zhang ZF, Fan SH (2009) Trace amounts of copper exacerbate beta amyloid-induced neurotoxicity in the cholesterol-fed mice through TNF-mediated inflammatory pathway. Brain Behav Immun 23:193–203. https://doi.org/10.1016/j.bbi.2008.09.003 CrossRefGoogle Scholar
- Poulaki V, Mitsiades CS, McMullan C, Fanourakis G, Negri J, Goudopoulou A, Halikias IX, Voutsinas G, Tseleni-Balafouta S, Miller JW, Mitsiades N (2005) Human retinoblastoma cells are resistant to apoptosis induced by death receptors: role of caspase-8 gene silencing. Invest Ophthalmol Vis Sci 46:358–366. https://doi.org/10.1167/iovs.04-0324 CrossRefGoogle Scholar
- Savva A, Roger T (2013) Targeting toll-like receptors: promising therapeutic strategies for the management of sepsis-associated pathology and infectious diseases. Front Immunol 4(387). https://doi.org/10.3389/fimmu.2013.00387
- Shahzad MN, Javed MT, Shabir S, Irfan M, Hussain R (2012) Effects of feeding urea and copper sulphate in different combinations on live body weight, carcass weight, percent weight to body weight of different organs and histopathological tissue changes in broilers. Exp Toxicol Pathol 64:141–147. https://doi.org/10.1016/j.etp.2010.07.009 CrossRefGoogle Scholar
- Sun X, Li J, Zhao H, Wang Y, Liu J, Shao Y, Xue Y, Xing M (2018) Synergistic effect of copper and arsenic upon oxidative stress, inflammation and autophagy alterations in brain tissues of Gallus gallus. J Inorg Biochem 178:54–62. https://doi.org/10.1016/j.jinorgbio.2017.10.006 CrossRefGoogle Scholar
- Wu MM, Lee CH, Hsu LI, Cheng WF, Lee TC, Wang YH, Chiou HY, Chen CJ (2016a) Effect of heme oxygenase-1 gene promoter polymorphism on cancer risk by histological subtype: a prospective study in arseniasis-endemic areas in Taiwan. Int J Cancer 138:1875–1886. https://doi.org/10.1002/ijc.29926 CrossRefGoogle Scholar
- Xiao C, He P, Han J, Tang M, Wang Z, Mi Y, Liu X (2018) 1,3-Dichloro-2-propanol evokes inflammation and apoptosis in BV-2 microglia via MAPKs and NF-kappaB signaling pathways mediated by reactive oxygen species. Toxicol Lett 284:103–112. https://doi.org/10.1016/j.toxlet.2017.12.011 CrossRefGoogle Scholar
- Yao HD, Wu Q, Zhang ZW, Zhang JL, Li S, Huang JQ, Ren FZ, Xu SW, Wang XL, Lei XG (2013a) Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks. J Nutr 143:613–619. https://doi.org/10.3945/jn.112.172395 CrossRefGoogle Scholar
- Zhao H, He Y, Li S, Sun X, Wang Y, Shao Y, Hou Z, Xing M (2017a) Subchronic arsenism-induced oxidative stress and inflammation contribute to apoptosis through mitochondrial and death receptor dependent pathways in chicken immune organs. Oncotarget 8:40327–40344Google Scholar