Biological Trace Element Research

, Volume 143, Issue 3, pp 1651–1665 | Cite as

The Protective Effects of Tea Polyphenols and Schisandrin B on Nephrotoxicity of Mercury

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


Mercury (Hg) is an occupational and environmental contaminant that is a well-recognized health hazard. To approach the concrete mechanisms of mercury nephrotoxicity and find out a new way to prevent it, the rats were subcutaneously injected with different dosages of mercuric chloride (HgCl2)—0, 2.2, 4.4, and 8.8 μmol/kg. The levels of Hg, blood urea nitrogen (BUN), urine protein, glutathione (GSH), malondialdehyde (MDA) and activities of N-acetyl-beta-d-glucosaminidase (NAG), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were investigated, and the levels of reactive oxygen species (ROS) and apoptosis and the pathological changes were also observed. In addition, the effects of 1 mmol/kg tea polyphenols (TP) and 0.04 mmol/kg schisandrin B (Sch B) were studied at 8.8 μmol/kg HgCl2. It was observed that the levels of Hg, BUN, urine protein, GSH, and MDA and activities of NAG, ALP, and LDH increased significantly; the activities of SOD and GSH-Px decreased significantly; the levels of ROS and apoptosis increased obviously; and many pathological changes occurred dose-dependently in the HgCl2 injection groups. Further investigation indicated that pretreatment with TP and Sch B significantly reversed the toxic effects of HgCl2. These results suggested that TP and Sch B might antagonize the nephrotoxicity caused by HgCl2 exposure.


Mercury Nephrotoxicity Oxidative damage Tea polyphenols Schisandrin B 



The authors thank Ming Zhao (Department of Occupational health, China Medical University), Miao Yu (Department of implement, China Medical University), and Jingyi Sun (The first affiliated hospital of China Medical University) for their technical assistance.


  1. 1.
    Tchounwou PB, Ayensu WK, Ninashvili N et al (2003) Environmental exposure to mercury and its toxicopathologic implications for public health. Environ Toxicol 18:149–175PubMedCrossRefGoogle Scholar
  2. 2.
    Bridges CC, Battle JR, Zalups RK (2007) Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells. Toxicol Appl Pharmacol 221:251–260PubMedCrossRefGoogle Scholar
  3. 3.
    Stacchiotti A, Borsani E, Rodella L et al (2003) Dose-dependent mercuric chloride tubular injury in rat kidney. Ultrastruct Pathol 27:253–259PubMedCrossRefGoogle Scholar
  4. 4.
    Stacchiotti A, Lavazza A, Rezzani R et al (2004) Mercuric chloride-induced alterations in stress protein distribution in rat kidney. Histol Histopathol 19:1209–1218PubMedGoogle Scholar
  5. 5.
    Sharma MK, Sharma A, Kumar A et al (2007) Evaluation of protective efficacy of Spirulina fusiformis against mercury induced nephrotoxicity in Swiss albino mice. Food Chem Toxicol 45:879–887PubMedCrossRefGoogle Scholar
  6. 6.
    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 45:543–550PubMedCrossRefGoogle Scholar
  7. 7.
    Miller DM, Lund BO, Woods SS (1991) Reactivity of Hg (II) with superoxide: evidence for the catalytic dismutation of superoxide by Hg (II). J Biochem Toxicol 6:293–298PubMedCrossRefGoogle Scholar
  8. 8.
    Fukasawa R, Kanda A, Hara S (2009) Anti-oxidative effects of rooibos tea extract on autoxidation and thermal oxidation of lipids. J Oleo Sci 58:275–283PubMedCrossRefGoogle Scholar
  9. 9.
    Christian H, Brian J, Shelby N et al (2008) Antioxidant effects of green tea and its polyphenols on bladder cells. Life Sci 83:12–18CrossRefGoogle Scholar
  10. 10.
    Li XY (1991) Bioactivity of neolignans from fructus Schizandrae. Mem Inst Oswaldo Cruz 86:31–37PubMedCrossRefGoogle Scholar
  11. 11.
    Chiu PY, Leung HY, Ko KM (2008) Schisandrin b enhances renal mitochondrial antioxidant status, functional and structural integrity, and protects against gentamicin-induced nephrotoxicity in rats. Biol Pharm Bull 31:602–605PubMedCrossRefGoogle Scholar
  12. 12.
    Chiu PY, Ko KM (2006) Schisandrin b-induced increase in cellular glutathione level and protection against oxidant injury are mediated by the enhancement of glutathione synthesis and regeneration in AML12 and H9c2 cells. Biofactors 26:221–230PubMedCrossRefGoogle Scholar
  13. 13.
    Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  14. 14.
    Spencer K (1986) Analytical reviews in clinical biochemistry: the estimation of creatinine. Ann Clin Biochem 23:1–25PubMedGoogle Scholar
  15. 15.
    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
  16. 16.
    Liau CY, Lin CS (2008) A modified coomassie brilliant blue G 250 staining method for the detection of chitinase activity and molecular weight after polyacrylamide gel electrophoresis. J Bio Sci Bio Eng 106:111–113Google Scholar
  17. 17.
    Buege JA, Aust SD (1978) Microsomal lipid peroxidation. J Meth Enzym 52:302–311CrossRefGoogle Scholar
  18. 18.
    Brescia F, Sarti M (2008) Modification to the Lampariello approach to evaluate reactive oxygen species production by flow cytometry. Cytom A 73:175–179CrossRefGoogle Scholar
  19. 19.
    Chun RL (2007) Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases. Int J Biochem Cell Biol 39:426–438CrossRefGoogle Scholar
  20. 20.
    Franko A, Budihna MV, Dodic-Fikfak M (2005) Long-term effect of elemental mercury on renal function in miners of the Idrija mercury mine. Ann Occup Hyg 49:521–527PubMedCrossRefGoogle Scholar
  21. 21.
    Kanda H, Kikushima M, Homma-Takeda S et al (2008) Downregulation of arginase II and renal apoptosis by inorganic mercury: overexpression of arginase II reduces its apoptosis. Arch Toxicol 82:67–73PubMedCrossRefGoogle Scholar
  22. 22.
    Edwards JR, Diamantakos EA, Peuler JD et al (2007) A novel method for the evaluation of proximal tubule epithelial cellular necrosis in the intact rat kidney using ethidium homodimer. BMC Physiol 7:1PubMedCrossRefGoogle Scholar
  23. 23.
    Zalups RK (2000) Molecular interactions with mercury in the kidney. Pharmacol Rev 52:113–143PubMedGoogle Scholar
  24. 24.
    Mahboob M, Shireen KF, Atkinson A et al (2001) Lipid peroxidation and antioxidant enzyme activity in different organs of mice exposed to low level of mercury. J Environ Sci Health 36:687–697CrossRefGoogle Scholar
  25. 25.
    Aleo MF, Morandini F, Bettoni F et al (2002) Antioxidant potential and gap junction-mediated intercellular communication as early biological markers of mercuric chloride toxicity in the MDCK cell line. Toxicol In Vitro 16:457–465PubMedCrossRefGoogle Scholar
  26. 26.
    Shimojo N, Kumagai Y, Nagafune J (2002) Difference between kidney and liver in decreased manganese superoxide dismutase activity caused by exposure of mice to mercuric chloride. Arch Toxicol 76:383–387PubMedCrossRefGoogle Scholar
  27. 27.
    Higdon JV, Frei B (2003) Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit Rev Food Sci Nutr 43:89–143PubMedCrossRefGoogle Scholar
  28. 28.
    Naasani I, Oh-Hashi F, Oh-Hara T et al (2003) Blocking telomerase by dietary polyphenols is a major mechanism for limiting the growth of human cancer cells in vitro and in vivo. Cancer Res 63:824–830PubMedGoogle Scholar
  29. 29.
    Yang CS, Lambert JD, Ju J et al (2007) Tea and cancer prevention: molecular mechanisms and human relevance. Toxicol Appl Pharmacol 224:265–273PubMedCrossRefGoogle Scholar
  30. 30.
    Yang CS, Lambert JD, Sang S et al (2009) Antioxidative and anti-carcinogenic activities of tea polyphenols. Arch Toxicol 83:11–21PubMedCrossRefGoogle Scholar
  31. 31.
    Chen N, Chiu PY, Kam KO (2008) Schisandrin B enhances cerebral mitochondrial antioxidant status and structural integrity, and protects against cerebral ischemia/reperfusion injury in rats. Biol Pharm Bull 31:1387–1391PubMedCrossRefGoogle Scholar
  32. 32.
    Chiu PY, Leung HY, Poon MK et al (2006) Chronic schisandrin B treatment improves mitochondrial antioxidant status and tissue heat shock protein production in various tissues of young adult and middle-aged rats. Biogerontology 7:199–210PubMedCrossRefGoogle Scholar
  33. 33.
    Chiu PY, Leung HY, Poon MK et al (2006) Schisandrin B induced antioxidant response is partly mediated by cytochrome P-4502E1 catalyzed reaction in mouse liver. Mol Cell Biochem 293:87–92PubMedCrossRefGoogle Scholar
  34. 34.
    Gegg ME, Beltran B, Salas-Pino S et al (2003) Differential effect of nitric oxide on glutathione metabolism and mitochondrial function in astrocytes and neurones: implications for neuroprotection/neurodegeneration? J Neurochem 86:228–237PubMedCrossRefGoogle Scholar
  35. 35.
    Wei D, Zhang XL, Wang YZ et al (2010) Lipid peroxidation levels, total oxidant status and superoxide dismutase in serum, saliva and gingival crevicular fluid in chronic periodontitis patients before and after periodontal therapy. Aust Dent J 55:70–78PubMedCrossRefGoogle Scholar
  36. 36.
    Jurczuk M, Moniuszko-Jakoniuk J, Brzoska MM (2006) Involvement of some low-molecular thiols in the peroxidative mechanisms of lead and ethanol action on rat liver and kidney. Toxicology 219:11–21PubMedCrossRefGoogle Scholar
  37. 37.
    Kedziora KZ, Luciak M, Blaszczyk J et al (1998) Effect of aminoguanidine on erythrocyte lipid peroxidation and activities of antioxidant enzymes in experimental diabetes. Clin Chem Lab Med 36:771–775CrossRefGoogle Scholar
  38. 38.
    Cadet J, Bellon S, Douki T et al (2004) Radiation-induced DNA damage: formation, measurement, and biochemical features. J Environ Pathol Toxicol Oncol 23:33–43PubMedCrossRefGoogle Scholar
  39. 39.
    Kannan K, Jain SK (2000) Oxidative stress and apoptosis. Pathophysiology 7:153–163PubMedCrossRefGoogle Scholar
  40. 40.
    Li L, Pan Q, Han W et al (2007) Schisandrin B prevents doxorubicin-induced cardiotoxicity via enhancing glutathione redox cycling. Clin Cancer Res 13:6753–6760PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

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

Personalised recommendations