Biological Trace Element Research

, Volume 146, Issue 2, pp 213–223

Effects of Lycopene and Proanthocyanidins on Hepatotoxicity Induced by Mercuric Chloride in Rats

  • Yu Deng
  • Zhaofa Xu
  • Wei Liu
  • Haibo Yang
  • Bin Xu
  • Yangang Wei


To evaluate the protective potential of lycopene (Lyc) and proanthocyanidins (PCs) against mercuric chloride (HgCl2)-induced hepatotoxicity, the study focused on the mechanism of oxidative stress. Firstly, the rats were subcutaneously (s.c.) injected with 0, 2.2, 4.4, and 8.8 μmol/kg HgCl2. Additionally, 40 mg/kg Lyc and 450 mg/kg PCs were given to the rats intragastrically (i.g.) before exposure to 8.8 μmol/kg HgCl2. Then, body weight, liver weight coefficient, mercury (Hg) contents, histological feature, ultrastructure, apoptosis, reactive oxygen species (ROS), glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA) in the liver were measured. Lactate dehydrogenase (LDH) and alanine transaminase (ALT) in serum were determined. After exposure to different concentrations of HgCl2,it was found that Hg contents, pathological and ultrastructure injury, activities of LDH and ALT, apoptosis, and levels of ROS, GSH, and MDA increased and the activities of SOD and GSH-Px decreased in a concentration-dependent manner. Further investigation found that pretreatment with Lyc and PCs inhibited ROS production, protected antioxidant enzymes, and reversed hepatotoxicity. We concluded that Lyc and PCs had hepatoprotective effects on HgCl2-induced toxicity by antagonizing oxidative stress in rat liver.


Mercury Lycopene Proanthocyanidins Hepatotoxicity Oxidative stress 


  1. 1.
    ATSDR (Agency for Toxic Substances and Disease Registry) (1999) Toxicological profile for mercury. US Department of Health and Human Services Public Health Service. Available at
  2. 2.
    Adams DH, Sonne C, Basu N et al (2010) Mercury contamination in spotted seatrout, Cynoscion nebulosus: an assessment of liver, kidney, blood, and nervous system health. Sci Total Environ 408(23):5808–5816PubMedCrossRefGoogle Scholar
  3. 3.
    Goering PL, Morgan DL, Ali SF (2002) Effects of mercury vapor inhalation on reactive oxygen species and antioxidant enzymes in rat brain and kidney are minimal. J Appl Toxicol 22(3):167–172PubMedCrossRefGoogle Scholar
  4. 4.
    Dutczak WJ, Ballatori N (1994) Transport of the glutathione–methylmercury complex across liver canalicular membranes on reduced glutathione carriers. J Biol Chem 269(13):9746–9751PubMedGoogle Scholar
  5. 5.
    Stohs SJ, Bagchi D (1995) Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 18(2):321–336PubMedCrossRefGoogle Scholar
  6. 6.
    McLaughlin JM, Olivo-Marston S, Vitolins MZ et al (2011) Effects of tomato- and soy-rich diets on the IGF-I hormonal network: a crossover study of postmenopausal women at high risk for breast cancer. Cancer Prev Res (Phila) 4(5):702–710CrossRefGoogle Scholar
  7. 7.
    Mordente A, Guantario B, Meucci E et al (2011) Lycopene and cardiovascular diseases: an update. Curr Med Chem 18(8):1146–1163PubMedCrossRefGoogle Scholar
  8. 8.
    Vlajinac H, Ilic M, Marinkovic J et al (2010) Nutrition and prostate cancer. J BUON 15(4):698–703PubMedGoogle Scholar
  9. 9.
    Quilliot D, Forbes A, Dubois F et al (2011) Carotenoid deficiency in chronic pancreatitis: the effect of an increase in tomato consumption. Eur J Clin Nutr 65(2):262–268PubMedCrossRefGoogle Scholar
  10. 10.
    Mortensen A, Skibsted LH, Sampson J et al (1997) Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants. FEBS Lett 418(1–2):91–97PubMedCrossRefGoogle Scholar
  11. 11.
    Schroeter H, Heiss C, Spencer JP et al (2010) Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs. Mol Aspects Med 31(6):546–557PubMedCrossRefGoogle Scholar
  12. 12.
    Rossi M, Rosato V, Bosetti C et al (2010) Flavonoids, proanthocyanidins, and the risk of stomach cancer. Cancer Causes Control 21(10):1597–1604PubMedCrossRefGoogle Scholar
  13. 13.
    Bobe G, Peterson JJ, Gridley G et al (2009) Flavonoid consumption and esophageal cancer among black and white men in the United States. Int J Cancer 125(5):1147–1154PubMedCrossRefGoogle Scholar
  14. 14.
    Karaaslan O, Ulusoy MG, Kankaya Y et al (2010) Protective effect of grape seed extract against ischaemia/reperfusion injury in a rat epigastricflap model. J Plast Reconstr Aesthet Surg 63(4):705–710PubMedCrossRefGoogle Scholar
  15. 15.
    Nichols JA, Katiyar SK (2010) Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res 302(2):71–83PubMedCrossRefGoogle Scholar
  16. 16.
    Yang H, Xu Z, Liu W et al (2011) The protective role of procyanidins and lycopene against mercuric chloride renal damage in rats. Biomed Environ Sci 24(5):56–61PubMedGoogle Scholar
  17. 17.
    Liu W, Xu Z, Yang H et al (2011) The protective effects of tea polyphenols and schisandrin B on nephrotoxicity of mercury. Biol Trace Elem Res (in press)Google Scholar
  18. 18.
    Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  19. 19.
    Stockwell PB, Corns WT (1993) The role of atomic fluorescence spectrometry in the automatic environmental monitoring of trace element analysis. J Automatic Chem 15:79–84CrossRefGoogle Scholar
  20. 20.
    Crowley LV (1967) The Reitman-Frankel colorimetric transaminase procedure in suspected myocardial infarction. Clin Chem 13(6):482–487PubMedGoogle Scholar
  21. 21.
    Weiss TS, Lichtenauer M, Kirchner S et al (2008) Hepatic progenitor cells from adult human livers for cell transplantation. Gut 57(8):1129–1138PubMedCrossRefGoogle Scholar
  22. 22.
    Li P, Feng XB, Qiu GL et al (2009) Mercury pollution in Asia: a review of the contaminated sites. J Hazard Mater 168(2–3):591–601PubMedCrossRefGoogle Scholar
  23. 23.
    Nwokocha CR, Owu DU, Ufearo CS et al (2011) Comparative study on the efficacy of Garcinia kola in reducing some heavy metal accumulation in liver of Wistar rats. J Ethnopharmacol 135(2):488–491PubMedCrossRefGoogle Scholar
  24. 24.
    Bridges CC, Joshee L, Zalups RK (2011) MRP2 and the handling of mercuric ions in rats exposed acutely to inorganic and organic species of mercury. Toxicol Appl Pharmacol 251(1):50–58PubMedCrossRefGoogle Scholar
  25. 25.
    Ung CY, Lam SH, Hlaing MM et al (2011) Mercury-induced hepatotoxicity in zebrafish: in vivo mechanistic insights from transcriptome analysis, phenotype anchoring and targeted gene expression validation. BMC Genomics 11:212CrossRefGoogle Scholar
  26. 26.
    Sener G, Sehirli O, Tozan A et al (2007) Ginkgo biloba extract protects against mercury(II)-induced oxidative tissue damage in rats. Food Chem Toxicol 45(4):543–550PubMedCrossRefGoogle Scholar
  27. 27.
    Patnaik BB, Roy A, Agarwal S et al (2010) Induction of oxidative stress by non-lethal dose of mercury in rat liver: possible relationships between apoptosis and necrosis. J Environ Biol 31(4):413–416PubMedGoogle Scholar
  28. 28.
    Blokhina O, Virolainen E, Fagerstedt KV (2002) Antioxidants, oxidative damage and oxygen deprivation stress: a review. Ann Bot 91:179–194CrossRefGoogle Scholar
  29. 29.
    Hoffman DJ, Eagles-Smith CA, Ackerman JT et al (2011) Oxidative stress response of Forster’s terns (Sterna forsteri) and Caspian terns (Hydroprogne caspia) to mercury and selenium bioaccumulation in liver, kidney, and brain. Environ Toxicol Chem 30(4):920–929PubMedCrossRefGoogle Scholar
  30. 30.
    Rao MV, Chhunchha B (2010) Protective role of melatonin against the mercury induced oxidative stress in the rat thyroid. Food Chem Toxicol 48(1):7–10PubMedCrossRefGoogle Scholar
  31. 31.
    Ji X, Wang W, Cheng J et al (2006) Free radicals and antioxidant status in rat liver after dietary exposure of environmental mercury. Environ Toxicol Pharmacol 22(3):309–314PubMedCrossRefGoogle Scholar
  32. 32.
    Cavusoglu K, Oruc E, Yapar K et al (2009) Protective effect of lycopene against mercury-induced cytotoxicity in albino mice: pathological evaluation. J Environ Biol 30(5 Suppl):807–814PubMedGoogle Scholar
  33. 33.
    Moselhy SS, Komousani TA (2011) Modulation of lead biohazards using a combination of epicatchin and lycopene in rats. Hum Exp Toxicol (in press)Google Scholar
  34. 34.
    Koul A, Arora N, Tanwar L (2010) Lycopene mediated modulation of 7,12 Dimethlybenz (a) anthracene induced hepatic clastogenicity in male Balb/c mice. Nutr Hosp 25(2):304–310PubMedGoogle Scholar
  35. 35.
    Huang CS, Hu ML (2011) Lycopene inhibits DNA damage and reduces hMTH1 mRNA expression in the liver of Mongolian gerbils treated with ferric nitrilotriacetate. Food Chem Toxicol 49(6):1381–1386PubMedCrossRefGoogle Scholar
  36. 36.
    Yousef MI, Saad AA, El-Shennawy LK (2009) Protective effect of grape seed proanthocyanidin extract against oxidative stress induced by cisplatin in rats. Food Chem Toxicol 47(6):1176–1183PubMedCrossRefGoogle Scholar
  37. 37.
    Bose KS, Agrawal BK (2007) Effect of lycopene from tomatoes (cooked) on plasma antioxidant enzymes, lipid peroxidation rate and lipid profile in grade-I hypertension. Ann Nutr Metab 51(5):477–481PubMedCrossRefGoogle Scholar
  38. 38.
    Bahcecioglu IH, Kuzu N, Metin K et al (2010) Lycopene prevents development of steatohepatitis in experimental nonalcoholic steatohepatitis model induced by high-fat diet. Vet Med Int. pii:262179Google Scholar
  39. 39.
    Lu Y, Zhao WZ, Chang Z, Chen WX, Li L (2004) Procyanidins from grape seeds protect against phorbol ester-induced oxidative cellular and genotoxic damage. Acta Pharmacol Sin 25(8):1083–1089PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Yu Deng
    • 1
  • Zhaofa Xu
    • 1
  • Wei Liu
    • 1
  • Haibo Yang
    • 1
  • Bin Xu
    • 1
  • Yangang Wei
    • 1
  1. 1.Department of Environmental Health, School of Public HealthChina Medical UniversityShenyangPeople’s Republic of China

Personalised recommendations