Antioxidant and Hepatoprotective Efficiency of Selenium Nanoparticles Against Acetaminophen-Induced Hepatic Damage


Overdoses of acetaminophen (APAP), a famous and widely used drug, may have hepatotoxic effects. Nanoscience is a novel scientific discipline that provides specific tools for medical science problems including using nano trace elements in hepatic diseases. Our study aimed to assess the hepatoprotective role of selenium nanoparticles (Nano-Se) against APAP-induced hepatic injury. Twenty-four male rats were classified into three equal groups: a control group that received 0.9 % NaCl, an APAP-treated group (oral administration), and a group treated with Nano-Se (10–20 nm, intraperitoneal (i.p.) injection) and APAP (oral administration). APAP overdose induced significant elevations in liver function biomarkers, hepatic lipid peroxidation, hepatic catalase, and superoxide dismutase (SOD), decreased the reduced glutathione (GSH) content and glutathione reductase (GR) activity, and stimulated significant DNA damage in hepatocytes, compared to control rats. Nano-Se administration improved the hepatic antioxidant protection mechanism and decreased cellular sensitivity to DNA fragmentation. Nano-Se exhibits a protective effect against APAP-induced hepatotoxicity through improved liver function and oxidative stress mediated by catalase, SOD, and GSH and decreases hepatic DNA fragmentation, a hepatic biomarker of cell death. Nano-Se could be a novel hepatoprotective strategy to inhibit oxidative stress.

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  1. 1.

    Burke A, Smyth EM, Fitzgerald GA (2006) Analgesic-antipyretic agents: pharmacotherapy of gout. In: Brunton LL, Lazo JS, Parker K (eds) Goodman and Gilman’s the Pharmacological Basis of Therapeutics, 11th edn. McGraw-Hill, New York, pp 671–716

    Google Scholar 

  2. 2.

    Bronstein AC, Spyker DA, Cantilena LR et al (2007) Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clin Toxicol (Phila) 8:815–917

    Article  Google Scholar 

  3. 3.

    Daly FF, Fountain JS, Murray L et al (2008) Guidelines for the management of paracetamol poisoning in Australia and New Zealand explanation and elaboration. A consensus statement from clinical toxicologists consulting to the Australasian poisons information centres. Med J Aust 188(5):296–301

    PubMed  Google Scholar 

  4. 4.

    Khashab M, Tector AJ, Kwo PY (2007) Epidemiology of acute liver failure. Curr Gastroenterol Rep 9(1):L:66–73

    Article  Google Scholar 

  5. 5.

    Larso AM, Polson J, Fontana RJ et al (2001) Acetaminophen sets record in the United States: number 1 analgesic and number 1 cause of acute liver failure. Hepatology 42:1364–1372

    Article  Google Scholar 

  6. 6.

    Rayman M (2002) The argument for increasing selenium intake. Proc Nutr Soc 61:203–215

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Flora SJS, Kannan GM, Pant BP, Jaiswal DK (2002) Combined administration of oxalic acid, succimer and its analogue for the reversal of gallium arsenide induced oxidative stress in rats. Arch Toxicol 76:269–276

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Imai HF, Hirao T, Sakamoto K et al (2003) Biochem Biophys Res Commun 305:278–286

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Zhang J, Gao X, Zhang L et al (2001) Biological effects of a nano red elemental selenium. BioFactors 15:27–38

    Article  PubMed  Google Scholar 

  10. 10.

    Ball P, Garwin L (1992) Science at the atomic scale. Nature 355:761–766

    Article  Google Scholar 

  11. 11.

    Huang B, Zhang J, Hou J et al (2003) Free radical scavenging efficiency of Nano-Se in vitro. Free Radic Biol Med 35:805–813

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Sieber F, Daziano JP, Günther WH et al (2005) Eemental selenium generated by the photobleaching of selenomerocyanine photosynthetizers forms conjugates with serum macromolecules that are toxic to tumer cells. Phosphorus Sulfur Silicon Relat Elem 180(3–4):647–657

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Zhang J, Wang H, Bao Y et al (2004) Nano red elemental selenium has no size effect in the induction of seleno-enzymes in both cultured cells and mice. Life Sci 75(2):237–244

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Oremland RS, Herbel MJ, Blum JS et al (2004) Structural and spectral features of selenium nanospheres produced by Se-respiring bacteria. Appl Environ Microbiol 70(1):52–60

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Wang R, Kong J, Wang D (2007) A survey of Chinese herbal ingredients with liver protection activities. Chinese Med 2:5

    Article  Google Scholar 

  16. 16.

    Mishra B, Hassan PA, Priyadarsini KI et al (2005) Reactions of biological oxidants with selenourea: formation of redox active nanoselenium. J Phys Chem B 109:12718–12723

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    El-Sayed WM, Aboul-Fadl T, Lamb JG et al (2006) Effect of selenium-containing compounds on hepatic chemoprotective enzymes in mice. Toxicology 220(2–3):179–88

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Taylor JB (2005) Time-dependent influence of supranutritional organically bound selenium on selenium accumulation in growing wether lambs. J Anim Sci 83:1186–1193

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Gao X, Zhang J, Zhang L (2000) Acute toxicity and bioavailability of nano red elemental selenium. Wei Sheng Yan Jiu 29(1):57–58

    CAS  PubMed  Google Scholar 

  20. 20.

    Zhang J, Wang H, Yan X et al (2005) Comparison of short-term toxicity between Nano-Se and selenite in mice. Life Sci 76(10):1099–109

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Viezeliene D, Jansen E, Rodovicius H et al (2011) Protective effect of selenium on aluminium-induced oxidative stress in mouse liver in vivo. Environ Toxicol Pharmacol 31:302–306

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Li Y, Li X, Wong YS et al (2011) The reversal of cisplatin-induced nephrotoxicity by selenium nanoparticles functionalized with 11-mercapto-1-undecanol by inhibition of ROS-mediated apoptosis. Biomaterials 32(34):9068–76

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Amin KA, Hassan MS, Awad ST et al (2011) The protective effects of cerium oxide nanoparticles against hepatic oxidative damage induced by monocrotaline. Int J Nanomedicine 6:143–9

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Peng D, Zhang J, Liu Q et al (2007) Size effect of selenium nanoparticles (Nano-Se) at supranutritional levels on selenium accumulation and glutathione S-transferase activity. J Inorg Biochem 101(10):1457–1463

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Jafari M, Rabbani A (2000) Dose and time dependent effects of caffeine on superoxide release, cell survival and DNA fragmentation of alveolar macrophages from rat lung. Toxicol 149(2e3):101e8

    Google Scholar 

  26. 26.

    Kanbur M, Eraslan G, Beyaz L et al (2009) The effects of royal jelly on liver damage induced by paracetamol in mice. Exp Toxicol Pathol 61(2):123–32

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Madkour FF, Abdel-Daim MM (2013) Hepatoprotective and antioxidant activity of Dunaliella salina in paracetamol-induced acute toxicity in rats. Indian J Pharm Sci 75:642–648

    PubMed  PubMed Central  Google Scholar 

  28. 28.

    Hajimehdipoor H, Sadeghi Z, Elmi S et al (2006) Protective effects of Swertia longifolia Boiss. and its active compound, swerchirin, on paracetamol-induced hepatotoxicity in mice. J Pharm Pharmacol 58:277–280

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Messarah M, Klibet F, Boumendjel A et al (2012) Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats. Exp Toxicol Pathol 64(3):167–74

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Ozardali I, Bitiren M, Karakilçik AZ et al (2004) Effects of selenium on histopathological and enzymatic changes in experimental liver injury of rats. Exp and Toxicol Pathol 56:59–64

    CAS  Article  Google Scholar 

  31. 31.

    Abdelmegeed MA, Moon KH, Chen C et al (2010) Role of cytochrome P450 2E1 in protein nitration and ubiquitin-mediated degradation during acetaminophen toxicity. Biochem Pharmacol 79(1):57–66

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Manimaran A, Sarkar SN, Sankar P (2010) Influence of repeated preexposure to arsenic on acetaminophen-induced oxidative stress in liver of male rats. Food and Chem Toxicol 48:605–610

    CAS  Article  Google Scholar 

  33. 33.

    Moling O, Cairon E, Rimenti G et al (2006) Hepatotoxicity after therapeutic doses of acetaminophen. Clin Ther 28:755–760

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Kim SN, Seo JY, Jung DW et al (2007) Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos 35:1754–1758

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Laine J, Auriola S, Pasanen M et al (2007) Acetaminophen bioactivation by CYP enzymes. Toxicol Lett 172:S85

    Article  Google Scholar 

  36. 36.

    Larson AM (2007) Acetaminophen hepatotoxicity. Clin Liver Dis 11:525–548

    Article  PubMed  Google Scholar 

  37. 37.

    Ghosh A, Sil PC (2007) Antioxidative effect of a protein from Cajanus indicus L. against Acetaminophen induced hepato-nephrotoxicity. J Biochem Mol Biol 40:1039–1049

    CAS  PubMed  Google Scholar 

  38. 38.

    Shi L, Wenjuan X, Wenbin Y et al (2011) Effect of sodium selenite, Se-yeast and nano-elemental selenium on growth performance, Se concentration and antioxidant status in growing male goats. Small Rumin Res 96:49–52

    Article  Google Scholar 

  39. 39.

    Ceconi CA, Boraso A, Ferrari CR (2003) Oxidative stress in cardiovascular disease. Arch Biochem Biophys 420:217–221

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Marczin NN, Elhabashi GS, Hoare RE et al (2003) Antioxidants in myocardial ischemia reperfusion injury therapeutic potential and basic mechanisms. Arch Biochem Biophys \:222–236

    Article  PubMed  Google Scholar 

  41. 41.

    Sodhi SA, Sharma APS, Brar RS et al (2008) Effect of a tocopherol and selenium on antioxidant status, lipid peroxidation and hepatopathy induced by malathion in chicks. Pesticide Biochem and Physiol 90(2):82–86

    CAS  Article  Google Scholar 

  42. 42.

    Ghosh A, Sil PC (2009) Protection of acetaminophen induced mitochondrial dysfunctions and hepatic necrosis via Akt-NF-B pathway: Role of a novel plant protein. Chemico-Biolog Interactions 177:96–106

    CAS  Article  Google Scholar 

  43. 43.

    Ramachandran A, Lebofsky M, Steven A et al (2011) The impact of partial manganese superoxide dismutase (SOD2)-deficiency on mitocho -ndrial oxidant stress, DNA fragmentation and liver injury during acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 25:226–233

    Article  Google Scholar 

  44. 44.

    Gujral JS, Knight TR, Farhood A et al (2002) Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis? Toxicol Sci 67:322–328

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Cover C, Mansouri A, Knight TR et al (2005) Peroxynitrite-induced mitochondrial and endonuclease-mediated nuclear DNA damage in acetaminophen hepatotoxicity. J Pharmacol Exp Ther 315:879–887

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Jaeschke H, Cover C, Bajt ML et al (2006) Role of caspases in acetaminophen-induced liver injury. Life Sci 78:1670–1676

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Zhang S, Luo Y, Zeng H et al (2011) Encapsulation of selenium in chitosan nanoparticles improves selenium availability and protects cells from selenium-induced DNA damage response. J Nutr Biochem 22(12):1137–1142

    Article  PubMed  Google Scholar 

  48. 48.

    Letavayová L, Vlcková V, Brozmanová J et al (2006) Selenium: From cancer prevention to DNA damage. Toxicology 227:1–14

    Article  PubMed  Google Scholar 

  49. 49.

    Hoeijmakers JH (2001) Genome maintenance mechanisms for preventing cancer. Nature 411:366–374

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Rafferty TS, Green MH, Lowe JE et al (2003) Effects of selenium compounds on induction of DNA damage by broadband ultraviolet radiation in human keratinocytes. Br J Dermatol 148:1001–1009

    CAS  Article  PubMed  Google Scholar 

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All authors carried out experimental work, statistical analysis, interpretation, and discussion of the results and wrote the paper related to their part of the work. All authors read and approved the final manuscript.

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Correspondence to Kamal Adel Amin.

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Amin, K.A., Hashem, K.S., Alshehri, F.S. et al. Antioxidant and Hepatoprotective Efficiency of Selenium Nanoparticles Against Acetaminophen-Induced Hepatic Damage. Biol Trace Elem Res 175, 136–145 (2017).

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  • Nano-Se
  • APAP
  • Hepatotoxicity
  • Oxidative stress
  • Histopathology