Abstract
The aim of this study is to investigate the effects of arsenic (As) and copper (Cu) on the inflammatory response, and the protective roles of heat shock proteins (Hsps) in chicken testes. Seventy-two 1-day-old male Hy-line chickens were treated with 30 mg/kg feed of arsenic trioxide (As2O3) and/or 300 mg/kg feed of copper sulfate (CuSO4) for 4, 8, and 12 weeks. The histological changes, inducible nitric oxide synthase (iNOS) activity, and the expressions of Hsps and inflammatory cytokines were detected. The results showed that slight histology changes were obvious in the testis tissue exposure to treatment groups. The activity and the protein level of iNOS were increased compared to the control group. The mRNA levels of proinflammatory cytokines and inflammatory factors were increased as a whole. However, anti-inflammatory cytokines were inhibited. The mRNA and protein levels of Hsp60, Hsp70, and Hsp90 were upregulated. These results suggested that sub-chronic exposure to As and/or Cu induced testicular poisoning in chickens. Increased Hsps tried to protect chicken testis tissues from tissues damage caused by inflammation. In conclusion, testicular poisoning induced by As and/or Cu caused inflammatory response and heat shock protein response in chicken testis tissues.
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Abdul KS, Jayasinghe SS, Chandana EP, Jayasumana C, De Silva PM (2015) Arsenic and human health effects: a review. Environ Toxicol Pharmacol 40(3):828–846. https://doi.org/10.1016/j.etap.2015.09.016
Adelibieke Y, Yisireyili M, Ng HY, Saito S, Nishijima F, Niwa T (2014) Indoxyl sulfate induces IL-6 expression in vascular endothelial and smooth muscle cells through OAT3-mediated uptake and activation of AhR/NF-kappaB pathway. Nephron Exp Nephrol 128(1-2):1–8. https://doi.org/10.1159/000365217
Al-Aqil A, Zulkifli I (2009) Changes in heat shock protein 70 expression and blood characteristics in transported broiler chickens as affected by housing and early age feed restriction. Poult Sci 88(7):1358–1364. https://doi.org/10.3382/ps.2008-00554
Bernabo P, Rebecchi L, Jousson O, Martinez-Guitarte JL, Lencioni V (2011) Thermotolerance and hsp70 heat shock response in the cold-stenothermal chironomid Pseudodiamesa branickii (NE Italy). Cell Stress Chaperones 16(4):403–410. https://doi.org/10.1007/s12192-010-0251-5
Cao H, Gao F, Xia B, Zhang M, Liao Y, Yang Z, Hu G, Zhang C (2016) 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
Carvalho LS, Panzoldo N, Santos SN, Modolo R, Almeida B, Quinaglia ESJ, Nadruz-Jr W, de Faria EC, Sposito AC (2014) HDL levels and oxidizability during myocardial infarction are associated with reduced endothelial-mediated vasodilation and nitric oxide bioavailability. Atherosclerosis 237(2):840–846. https://doi.org/10.1016/j.atherosclerosis.2014.10.103
Chatterjee S, Sarkar S, Bhattacharya S (2014) Toxic metals and autophagy. Chem Res Toxicol 27(11):1887–1900. https://doi.org/10.1021/tx500264s
Csermely P, Schnaider T, Soti C, Prohaszka Z, Nardai G (1998) The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol Ther 79(2):129–168. https://doi.org/10.1016/S0163-7258(98)00013-8
Dale N (1994) National Research Council nutrient requirements of poultry—ninth revised edition (1994). J Appl Poult Res 3(1):101–101. https://doi.org/10.1093/japr/3.1.101
Du Y, Zhu Y, Teng X, Zhang K, Teng X, Li S (2015) Toxicological effect of manganese on NF-kappaB/iNOS-COX-2 signaling pathway in chicken testes. Biol Trace Elem Res 168(1):227–234. https://doi.org/10.1007/s12011-015-0340-5
Duan D, Zhang S, Li X, Guo H, Chen M, Zhang Y, Han J, Lv Y (2014) Activation of the TLR/MyD88/NF-kappaB signal pathway contributes to changes in IL-4 and IL-12 production in piglet lymphocytes infected with porcine circovirus type 2 in vitro. PLoS One 9(5):e97653. https://doi.org/10.1371/journal.pone.0097653
Epanchintsev A, Shyamsunder P, Verma RS, Lyakhovich A (2015) IL-6, IL-8, MMP-2, MMP-9 are overexpressed in Fanconi anemia cells through a NF-kappaB/TNF-alpha dependent mechanism. Mol Carcinog 54(12):1686–1699. https://doi.org/10.1002/mc.22240
Felley-Bosco E, Bender F, Quest AF (2002) Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells. Biol Res 35(2):169–176
Festa RA, Thiele DJ (2011) Copper: an essential metal in biology. Curr Biol 21(21):R877–R883. https://doi.org/10.1016/j.cub.2011.09.040
Guo H, Deng H, Cui H, Peng X, Fang J, Zuo Z, Deng J, Wang X, Wu B, Chen K (2015) Nickel chloride (NiCl2)-caused inflammatory responses via activation of NF-kappaB pathway and reduction of anti-inflammatory mediator expression in the kidney. Oncotarget 6(30):28607–28620. https://doi.org/10.18632/oncotarget.5759
Guo Y, Zhao P, Guo G, Hu Z, Tian L, Zhang K, Sun Y, Zhang X, Zhang W, Xing M (2016) Effects of arsenic trioxide exposure on heat shock protein response in the immune organs of chickens. Biol Trace Elem Res 169(1):134–141. https://doi.org/10.1007/s12011-015-0389-1
Han DM, Choi MR, Jung KH, Lee HT, Park JH, Ohn T, Chai YG (2012) Proteomic analysis of the copper ion-induced stress response in a human embryonic carcinoma cell line. Int J Toxicol 31(4):397–406. https://doi.org/10.1177/1091581812446869
He X, Liu W, Shi M, Yang Z, Zhang X, Gong P (2017) Docosahexaenoic acid attenuates LPS-stimulated inflammatory response by regulating the PPARgamma/NF-kappaB pathways in primary bovine mammary epithelial cells. Res Vet Sci 112:7–12. https://doi.org/10.1016/j.rvsc.2016.12.011
Hseu YC, Wu FY, Wu JJ, Chen JY, Chang WH, Lu FJ, Lai YC, Yang HL (2005) Anti-inflammatory potential of Antrodia camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-kappaB pathway. Int Immunopharmacol 5(13-14):1914–1925. https://doi.org/10.1016/j.intimp.2005.06.013
Hughes MF, Beck BD, Chen Y, Lewis AS, Thomas DJ (2011) Arsenic exposure and toxicology: a historical perspective. Toxicol Sci 123(2):305–332. https://doi.org/10.1093/toxsci/kfr184
Jiang Y, Wang X, Guo Y, Li W, Yang S, Li W, Cai W (2015) Expression of heat shock protein 27 in benign prostatic hyperplasia with chronic inflammation. Med Sci Monit 21:2976–2985. https://doi.org/10.12659/MSM.894562
Jung WK, Choi I, Lee DY, Yea SS, Choi YH, Kim MM, Park SG, Seo SK, Lee SW, Lee CM, Park YM, Choi IW (2008) Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 macrophages via the p38/ERK and NF-kappaB pathways. Int J Biochem Cell Biol 40(11):2572–2582. https://doi.org/10.1016/j.biocel.2008.05.005
Kim BE, Nevitt T, Thiele DJ (2008) Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol 4(3):176–185. https://doi.org/10.1038/nchembio.72
Kraemer LD, Campbell PG, Hare L (2005) Dynamics of Cd, Cu and Zn accumulation in organs and sub-cellular fractions in field transplanted juvenile yellow perch (Perca flavescens). Environ Pollut 138(2):324–337. https://doi.org/10.1016/j.envpol.2005.03.006
Ledoux DR, Henry PR, Ammerman CB, Rao PV, Miles RD (1991) Estimation of the relative bioavailability of inorganic copper sources for chicks using tissue uptake of copper. J Anim Sci 69(1):215–222. https://doi.org/10.2527/1991.691215x
Li X, Xing M, Chen M, Zhao J, Fan R, Zhao X, Cao C, Yang J, Zhang Z, Xu S (2017) 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
Liu G, Wang ZK, Wang ZY, Yang DB, Liu ZP, Wang L (2016b) 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(5):1193–1209. https://doi.org/10.1007/s00204-015-1547-0
Liu L, Fu C, Yan M, Xie H, Li S, Yu Q, He S, He J (2016a) Resveratrol modulates intestinal morphology and HSP70/90, NF-kappaB and EGF expression in the jejunal mucosa of black-boned chickens on exposure to circular heat stress. Food Funct 7(3):1329–1338. https://doi.org/10.1039/C5FO01338K
Liu L, Yang B, Cheng Y, Lin H (2015) Ameliorative effects of selenium on cadmium-induced oxidative stress and endoplasmic reticulum stress in the chicken kidney. Biol Trace Elem Res 167(2):308–319. https://doi.org/10.1007/s12011-015-0314-7
Liu SX, Athar M, Lippai I, Waldren C, Hei TK (2001) Induction of oxyradicals by arsenic: implication for mechanism of genotoxicity. Proc Natl Acad Sci U S A 98(4):1643–1648. https://doi.org/10.1073/pnas.98.4.1643
Liu XF, Li ZP, Tie F, Liu N, Zhang ZW, SW X (2013) Effects of manganese-toxicity on immune-related organs of cocks. Chemosphere 90(7):2085–2100. https://doi.org/10.1016/j.chemosphere.2012.10.072
Ma Y, Ma Z, Yin S, Yan X, Wang J (2017) Arsenic and fluoride induce apoptosis, inflammation and oxidative stress in cultured human umbilical vein endothelial cells. Chemosphere 167:454–461. https://doi.org/10.1016/j.chemosphere.2016.10.025
Mocchegiani E, Costarelli L, Giacconi R, Piacenza F, Basso A, Malavolta M (2012) Micronutrient (Zn, cu, Fe)–gene interactions in ageing and inflammatory age-related diseases: implications for treatments. Ageing Res Rev 11(2):297–319. https://doi.org/10.1016/j.arr.2012.01.004
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(3):295–302. https://doi.org/10.1289/ehp.1205875
Pereira TC, Campos MM, Bogo MR (2016) Copper toxicology, oxidative stress and inflammation using zebrafish as experimental model. J Appl Toxicol 36(7):876–885. https://doi.org/10.1002/jat.3303
Pi K, Wang Y, Xie X, Su C, Ma T, Li J, Liu Y (2015) Hydrogeochemistry of co-occurring geogenic arsenic, fluoride and iodine in groundwater at Datong Basin, northern China. J Hazard Mater 300:652–661. https://doi.org/10.1016/j.jhazmat.2015.07.080
Scheiber I, Dringen R, Mercer JF (2013) Copper: effects of deficiency and overload. Met Ions Life Sci 13:359–387. https://doi.org/10.1007/978-94-007-7500-8_11
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(3):141–147. https://doi.org/10.1016/j.etp.2010.07.009
Singh AP, Goel RK, Kaur T (2011) Mechanisms pertaining to arsenic toxicity. Toxicol Int 18(2):87–93. https://doi.org/10.4103/0971-6580.84258
Sreedhar AS, Csermely P (2004) Heat shock proteins in the regulation of apoptosis: new strategies in tumor therapy: a comprehensive review. Pharmacol Ther 101(3):227–257. https://doi.org/10.1016/j.pharmthera.2003.11.004
Sun H, Wu W, Guo J, Xiao R, Jiang F, Zheng L, Zhang G (2016) Effects of nickel exposure on testicular function, oxidative stress, and male reproductive dysfunction in Spodoptera litura Fabricius. Chemosphere 148:178–187. https://doi.org/10.1016/j.chemosphere.2015.10.068
Waisberg M, Joseph P, Hale B, Beyersmann D (2003) Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 192(2-3):95–117. https://doi.org/10.1016/S0300-483X(03)00305-6
Wang G, Zhang T, Sun W, Wang H, Yin F, Wang Z, Zuo D, Sun M, Zhou Z, Lin B, Xu J, Hua Y, Li H, Cai Z (2017b) Arsenic sulfide induces apoptosis and autophagy through the activation of ROS/JNK and suppression of Akt/mTOR signaling pathways in osteosarcoma. Free Radic Biol Med 106:24–37. https://doi.org/10.1016/j.freeradbiomed.2017.02.015
Wang L, Ren L, Tang T, Dai K, Yang K, Hao Y (2015) A novel nano-copper-bearing stainless steel with reduced Cu(2+) release only inducing transient foreign body reaction via affecting the activity of NF-kappaB and caspase 3. Int J Nanomedicine 10:6725–6739. https://doi.org/10.2147/IJN.S90249
Wang LL, Liu T, Wang C, Zhao FQ, Zhang ZW, Yao HD, Xing HJ, SW X (2013) Effects of atrazine and chlorpyrifos on the production of nitric oxide and expression of inducible nitric oxide synthase in the brain of common carp (Cyprinus carpio L.) Ecotoxicol Environ Saf 93:7–12. https://doi.org/10.1016/j.ecoenv.2013.03.007
Wang Y, Wang K, Huang H, Gu X, Teng X (2017a) Alleviative effect of selenium on inflammatory damage caused by lead via inhibiting inflammatory factors and heat shock proteins in chicken testes. Environ Sci Pollut Res Int 24(15):13405–13413. https://doi.org/10.1007/s11356-017-8785-z
Warner N, Burberry A, Pliakas M, McDonald C, Nunez G (2014) A genome-wide small interfering RNA (siRNA) screen reveals nuclear factor-kappaB (NF-kappaB)-independent regulators of NOD2-induced interleukin-8 (IL-8) secretion. J Biol Chem 289(41):28213–28224. https://doi.org/10.1074/jbc.M114.574756
Yan M, Hou M, Liu J, Zhang S, Liu B, Wu X, Liu G (2017) Regulation of iNOS-derived ROS generation by HSP90 and Cav-1 in porcine reproductive and respiratory syndrome virus-infected swine lung injury. Inflammation 40(4):1236–1244. https://doi.org/10.1007/s10753-017-0566-9
Yao HD, Wu Q, Zhang ZW, Li S, Wang XL, Lei XG, Xu SW (2013a) Selenoprotein W serves as an antioxidant in chicken myoblasts. Biochim Biophys Acta 1830(4):3112–3120. https://doi.org/10.1016/j.bbagen.2013.01.007
Yao HD, Wu Q, Zhang ZW, Zhang JL, Li S, Huang JQ, Ren FZ, SW X, Wang XL, Lei XG (2013b) Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks. J Nutr 143(5):613–619. https://doi.org/10.3945/jn.112.172395
Zhang K, Zhao P, Guo G, Guo Y, Tian L, Sun X, Li S, He Y, Sun Y, Chai H, Zhang W, Xing M (2016b) Arsenic trioxide attenuates NF-kappaB and cytokine mRNA levels in the livers of cocks. Biol Trace Elem Res 170(2):432–437. https://doi.org/10.1007/s12011-015-0455-8
Zhang QF, Li YW, Liu ZH, Chen QL (2016a) Reproductive toxicity of inorganic mercury exposure in adult zebrafish: histological damage, oxidative stress, and alterations of sex hormone and gene expression in the hypothalamic–pituitary–gonadal axis. Aquat Toxicol 177:417–424. https://doi.org/10.1016/j.aquatox.2016.06.018
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(1):224–236. https://doi.org/10.1007/s12011-015-0462-9
Zhu Q, Xu X, Liu X, Lin J, Kan Y, Zhong Y, Liu F, Xu J (2015) Sodium houttuyfonate inhibits inflammation by blocking the MAPKs/NF-kappaB signaling pathways in bovine endometrial epithelial cells. Res Vet Sci 100:245–251. https://doi.org/10.1016/j.rvsc.2015.04.004
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This study was supported by the National Natural Science Foundation of China (grant no. 31672619), the Fundamental Research Funds for the Central Universities (grant no. 2572016EAJ5), and the Natural Science Foundation of Heilongjiang Province (grant no. C2015061).
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Shao, Y., Zhao, H., Wang, Y. et al. 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, 7719–7729 (2018). https://doi.org/10.1007/s11356-017-1042-7
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DOI: https://doi.org/10.1007/s11356-017-1042-7