Effect of Selenium on the Levels of Cytokines and Trace Elements in Toxin-Mediated Oxidative Stress in Male Rats


Selenium is an essential cofactor in the key enzymes involved in cellular antioxidant defense. This study was designed to investigate the protective effects of selenium on mercury chloride (HgCl2)-induced toxicity. Male Wistar rats were randomly divided into four groups of six animals each. The first group was control; the second group was treated with mercuric chloride (HgCl2: 50 mg/kg/bw). The third group was treated with sodium selenite (Se 0.2 mg/kg/bw), and the fourth group received Se (0.2 mg/kg/bw) plus HgCl2 (50 mg/kg for 24 h). The influence of Se on mercury induced levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) and zinc, copper, and iron in serum of rats were observed. The serum MDA, SOD, zinc, and iron concentrations were found to be statistically different among the control and toxin-treated group. The serum levels of IL-6, IL-10, and TNF-α were also measured. There was a significant decrease in the levels of TNF-α, IL-6, and IL-10 in toxin-treated group II compared with that of the control group (p < 0.05). A significant increase in the serum levels of inflammatory cytokines IL-6, TNF-α, and IL-10 after administration of Se seemed to counteract some of the damage, as indicated by differences in the serum concentrations of major elements.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2


  1. 1.

    Clarkson TW, Magos L (2006) The toxicology of mercury and its chemical compounds. Crit Rev Toxicol 36:609–662

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Rao MV, Chhunchha B (2010) Protective role of melatonin against the mercury induced oxidative stress in the rat thyroid. Food Chem Toxicol 48:7–10

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Agarwal R, Raisuddin S, Tewari S, Goel SK, Raizada RB, Behari JR (2010a) Evaluation of comparative effect of pre- and posttreatment of selenium on mercury-induced oxidative stress, histological alterations, and metallothionein mRNA expression in rats. J Biochem Mol Toxicol 24:123–135

    PubMed  CAS  Google Scholar 

  4. 4.

    El-Shenawy SM, Hassan NS (2008) Comparative evaluation of the protective effect of selenium and garlic against liver and kidney damage induced by mercury chloride in the rats. Pharmacol Rep 60:199–208

    PubMed  CAS  Google Scholar 

  5. 5.

    Magos L, Clarkson TW (2006) Overview of the clinical toxicity of mercury. Ann Clin Biochem 43:257–268

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Agarwal R, Kumar R, Behari JR (2007) Mercury and lead content in fish species from the river Gomti, Lucknow, India, as biomarkers of contamination. Bull Environ Contam Toxicol 78:118–122

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Lucena GM, Franco JL, Ribas CM, Azevedo MS, Meotti FC, Gadotti VM, et al. (2007) Cipura paludosa extract prevents methyl mercury-induced neurotoxicity in mice. Basic Clin Pharmacol Toxicol 101:127–131

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Taber KH, Hurley RA (2008) Mercury exposure: effects across the lifespan. J Neuropsychiatry Clin Neurosci 20:iv–389

    Google Scholar 

  9. 9.

    Liu WW, Jiang CQ, Hu ZB, Zhang C, Xu QR, Zhou G (2006) Mercury concentration in cerebrospinal fluid in patients with chronic mercury poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za ZhiZhonghua Laodong Weisheng Zhiyebing Zazhi Chin J Ind Hyg Occup Dis 24:403–405

    CAS  Google Scholar 

  10. 10.

    Farina M, Franco JL, Ribas CM, Meotti FC, Missau FC, Pizzolatti MG, et al. (2005) Protective effects of Polygala paniculata extract against methylmercury-induced neurotoxicity in mice. J Pharm Pharmacol 57:1503–1508

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Clarkson TW (1997) The toxicology of mercury. Crit Rev Clin Lab Sci 34:369–403

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Li Z, Wu J, Deleo CJ (2006) RNA damage and surveillance under oxidative stress. IUBMB Life 58:581–588

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Patrick L (2002) Mercury toxicity and antioxidants: part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev 7:456–471

    PubMed  Google Scholar 

  14. 14.

    Pillai A, Gupta S (2005) Antioxidant enzyme activity and lipid peroxidation in liver of female rats co-exposed to lead and cadmium: effects of vitamin E and Mn2+. Free Radic Res 39:707–712

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Agarwal R, Goel SK, Chandra R, Behari JR (2010b) Role of vitamin E in preventing acute mercury toxicity in rat. Environ Toxicol Pharmacol 29:70–78

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Ahn CB, Song CH, Kim WH, Kim YK (2002) Effects of Juglans sinensis Dode extract and antioxidant on mercury chloride-induced acute renal failure in rabbits. J Ethnopharmacol 82:45–49

    PubMed  Article  Google Scholar 

  17. 17.

    Nava M, Romero F, Quiroz Y, Parra G, Bonet L, Rodriguez-Iturbe B (2000) Melatonin attenuates acute renal failure and oxidative stress induced by mercuric chloride in rats. Am J Physiol Ren Physiol 279:F910–F918

    CAS  Google Scholar 

  18. 18.

    Gado AM, Aldahmash BA (2013) Antioxidant effect of Arabic gum against mercuric chloride-induced nephrotoxicity. Drug Des Devel Ther 7:1245–1252

    PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Kumar D, Singh S, Singh AK, Rizvi SI (2013) Pomegranate (Punica granatum) peel extract provides protection against mercuric chloride-induced oxidative stress in Wistar strain rats. Pharm Biol 51:441–446

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Tanguy S, Boucher F, Besse S, Toufektsian MC, Ducros V, Favier A, et al. (1999) Oral selenium supplementation in rats does not protect isolated rings of aorta against exogenous hydrogen peroxide. J Trace Elem Med Biol 13:238–241

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Kouba A, Velisek J, Stara A, Masojidek J, Kozak P (2014) Supplementation with sodium selenite and selenium-enriched microalgae biomass show varying effects on blood enzymes activities, antioxidant response, and accumulation in common barbel (Barbus barbus). Biomed Res Int 2014:408270

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  22. 22.

    Song E, Su C, Fu J, Xia X, Yang S, Xiao C, et al. (2014) Selenium supplementation shows protective effects against patulin-induced brain damage in mice via increases in GSH-related enzyme activity and expression. Life Sci 109:37–43

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Ghadi FE, Ghara AR, Bhattacharyya S, Dhawan DK (2009) Selenium as a chemopreventive agent in experimentally induced colon carcinogenesis. World J Gastrointest Oncol 1:74–81

    PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Agarwal R, Behari JR (2007a) Role of selenium in mercury intoxication in mice. Ind Health 45:388–395

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Erkekoglu P, Rachidi W, De Rosa V, Giray B, Favier A, Hincal F (2010) Protective effect of selenium supplementation on the genotoxicity of di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate treatment in LNCaP cells. Free Radic Biol Med 49:559–566

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Bosse AC, Pallauf J, Hommel B, Sturm M, Fischer S, Wolf NM, et al. (2010) Impact of selenite and selenate on differentially expressed genes in rat liver examined by microarray analysis. Biosci Rep 30:293–306

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Yu X, Xu X, Su J (2008) Protective effects of nanometer selenium on acute gastric mucosal lesion in rats. Wei Sheng Yan Jiu 37:594–596

    PubMed  CAS  Google Scholar 

  28. 28.

    Micke O, Schomburg L, Buentzel J, Kisters K, Muecke R (2009) Selenium in oncology: from chemistry to clinics. Molecules 14:3975–3988

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Dziaman T, Huzarski T, Gackowski D, Rozalski R, Siomek A, Szpila A, et al. (2009) Selenium supplementation reduced oxidative DNA damage in adnexectomized BRCA1 mutations carriers. Cancer Epidemiol Biomark Prev 18:2923–2928

    Article  CAS  Google Scholar 

  30. 30.

    Su L, Wang M, Yin ST, Wang HL, Chen L, Sun LG, et al. (2008) The interaction of selenium and mercury in the accumulations and oxidative stress of rat tissues. Ecotoxicol Environ Saf 70:483–489

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Agarwal R, Behari JR (2007b) Effect of selenium pretreatment in chronic mercury intoxication in rats. Bull Environ Contam Toxicol 79:306–310

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Diplock AT, Watkins WJ, Hewison M (1986) Selenium and heavy metals. Ann Clin Res 18:55–60

    PubMed  CAS  Google Scholar 

  33. 33.

    Goyer RA (1995) Nutrition and metal toxicity. Am J Clin Nutr 61:646S–650S

    PubMed  CAS  Google Scholar 

  34. 34.

    Goyer RA, Cherian MG, Jones MM, Reigart JR (1995) Role of chelating agents for prevention, intervention, and treatment of exposures to toxic metals. Environ Health Perspect 103:1048–1052

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  35. 35.

    El-Demerdash FM (2004) Antioxidant effect of vitamin E and selenium on lipid peroxidation, enzyme activities and biochemical parameters in rats exposed to aluminium. J Trace Elem Med Biol 18:113–121

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    PubMed  CAS  Google Scholar 

  38. 38.

    Uzunhisarcikli M, Aslanturk A, Kalender S, Apaydin FG, Bas H (2015) Mercuric chloride induced hepatotoxic and hematologic changes in rats: the protective effects of sodium selenite and vitamin E. Toxicol Ind Health

  39. 39.

    Kalender S, Uzun FG, Demir F, Uzunhisarcikli M, Aslanturk A (2013) Mercuric chloride-induced testicular toxicity in rats and the protective role of sodium selenite and vitamin E. Food Chem Toxicol 55:456–462

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Frouin H, Loseto LL, Stern GA, Haulena M, Ross PS (2012) Mercury toxicity in beluga whale lymphocytes: limited effects of selenium protection. Aquat Toxicol 109:185–193

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Blanusa M, Orct T, Vihnanek Lazarus M, Sekovanic A, Piasek M (2012) Mercury disposition in suckling rats: comparative assessment following parenteral exposure to thiomersal and mercuric chloride. J Biomed Biotechnol 2012:256965

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  42. 42.

    Yu D, Zhang ZW, Yao HD, Li S, Xu SW (2014) Antioxidative role of selenoprotein W in oxidant-induced chicken splenic lymphocyte death. Biometals 27:277–291

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Joshi D, Mittal DK, Shukla S, Srivastav AK, Srivastav SK (2014) N-acetyl cysteine and selenium protects mercuric chloride-induced oxidative stress and antioxidant defense system in liver and kidney of rats: a histopathological approach. J Trace Elem Med Biol 28:218–226

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Azevedo BF, Futuro Neto Hde A, Stefanon I, Vassallo DV (2011) Acute cardiorespiratory effects of intracisternal injections of mercuric chloride. Neurotoxicology 32:350–354

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Pal M, Ghosh M (2012) Studies on comparative efficacy of alpha-linolenic acid and alpha-eleostearic acid on prevention of organic mercury-induced oxidative stress in kidney and liver of rat. Food Chem Toxicol 50:1066–1072

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Houston MC (2011) Role of mercury toxicity in hypertension, cardiovascular disease, and stroke. J Clin Hypertens (Greenwich) 13:621–627

    Article  CAS  Google Scholar 

  47. 47.

    Zhu X, Guo K, Lu Y (2011) Selenium effectively inhibits 1,2-dihydroxynaphthalene-induced apoptosis in human lens epithelial cells through activation of PI3-K/Akt pathway. Mol Vis 17:2019–2027

    PubMed  PubMed Central  CAS  Google Scholar 

  48. 48.

    Taskin E, Dursun N (2012) The protection of selenium on adriamycin-induced mitochondrial damage in rat. Biol Trace Elem Res 147:165–171

    PubMed  Article  CAS  Google Scholar 

  49. 49.

    Liu Y, Li BH, Sun XM, Lin AH, Wang DB (2012) Effect of selenium on the interaction between daunorubicin and cardiac myosin. Biol Trace Elem Res 147:240–245

    PubMed  Article  CAS  Google Scholar 

  50. 50.

    Dong JZ, Wang Y, Wang SH, Yin LP, Xu GJ, Zheng C, et al. (2013) Selenium increases chlorogenic acid, chlorophyll and carotenoids of Lycium chinense leaves. J Sci Food Agric 93:310–315

    PubMed  Article  CAS  Google Scholar 

  51. 51.

    Yilmaz DM, Haciyakupoglu E, Haciyakupoglu S, Polat S, Ozgur H, Sencar L, et al. (2011) Effects of sodium selenite and amiloride on calvarial calcification in closing small cranial defects. J Neurosurg 114:478–484

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Shi D, Guo S, Liao S, Su R, Guo M, Liu N, et al. (2012) Protection of selenium on hepatic mitochondrial respiratory control ratio and respiratory chain complex activities in ducklings intoxicated with aflatoxin B(1). Biol Trace Elem Res 145:312–317

    PubMed  Article  CAS  Google Scholar 

  53. 53.

    Dong JZ, Lei C, Ai XR, Wang Y (2012) Selenium enrichment on Cordyceps militaris link and analysis on its main active components. Appl Biochem Biotechnol 166:1215–1224

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    Chen YC, Prabhu KS, Das A, Mastro AM (2013) Dietary selenium supplementation modifies breast tumor growth and metastasis. Int J Cancer 133:2054–2064

    PubMed  Article  CAS  Google Scholar 

  55. 55.

    Schwartz LH, Urban T, Hercberg S (1994) Antioxidant minerals and vitamins. Role in cancer prevention. Presse Med 23:1826–1830

    PubMed  CAS  Google Scholar 

  56. 56.

    Ognjanovic BI, Markovic SD, Pavlovic SZ, Zikic RV, Stajn AS, Saicic ZS (2008) Effect of chronic cadmium exposure on antioxidant defense system in some tissues of rats: protective effect of selenium. Physiol Res 57:403–411

    PubMed  CAS  Google Scholar 

  57. 57.

    Yang H, Xu Z, Liu W, Deng Y, Xu B (2011) The protective role of procyanidins and lycopene against mercuric chloride renal damage in rats. Biomed Environ Sci 24:550–559

    PubMed  CAS  Google Scholar 

  58. 58.

    Leal ML, de Camargo EV, Ross DH, Molento MB, Lopes ST, da Rocha JB (2010) Effect of selenium and vitamin E on oxidative stress in lambs experimentally infected with Haemonchus contortus. Vet Res Commun 34:549–555

    PubMed  Article  Google Scholar 

Download references


This research project was supported by the “Research Center of the Center for Female Scientific and Medical Colleges,” Deanship of Scientific Research, King

, Saud University, Riyadh, Saudi Arabia.

Author information



Corresponding author

Correspondence to S. Ansar.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ansar, S. Effect of Selenium on the Levels of Cytokines and Trace Elements in Toxin-Mediated Oxidative Stress in Male Rats. Biol Trace Elem Res 169, 129–133 (2016). https://doi.org/10.1007/s12011-015-0403-7

Download citation


  • Selinium
  • Serum
  • Toxicity
  • Trace elements
  • Inflammation
  • Cytokines