Skip to main content
SpringerLink
Log in

Liver Injury and Its Molecular Mechanisms in Mice Caused by Exposure to Cerium Chloride

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

Cerium has been demonstrated to damage liver of mice, but very little is known about the molecular mechanisms underlying the mouse liver apoptosis. In order to understand the liver injury induced by intragastric administration of cerium chloride (CeCl3) for 60 consecutive days, the hepatocyte ultrasrtucture, various oxidative stress parameters, and the stress-related gene expression levels were investigated for the mouse liver. The results demonstrated that CeCl3 had an obvious accumulation in the mouse liver, leading to a classical laddering cleavage of DNA and hepatocyte apoptosis. CeCl3 significantly promoted the accumulation of reactive oxygen species and inhibited the stress-related gene expression of superoxide dismutase, catalase, glutathione peroxidase, metallothionein, heat-shock protein 70, glutathione-S-transferase, P53, and transferring, and it effectively activated the cytochrome p450 1A. It implied that CeCl3 resulted in apoptosis and alteration of expression levels of the genes related with metal detoxification/metabolism regulation and radical scavenging action in mice.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Barata C, Lekumberri I, Vila-Escale M, Prat N, Porte C (2005) Trace metal concentration, antioxidant enzyme activities and susceptibility to oxidative stress in the tricoptera larvae Hydropsyche exocellata from the Llobregat river basin (NE Spain). Aquat Toxicol 74:3–19

    Article  CAS  Google Scholar 

  • Basu A, Chakrabarty K, Chatterjee GC (1984) The effects of lanthanum chloride administration in newborn chicks on glutamate uptake and release by brain synaptosomes. Toxicol Lett 20:303–308

    Article  CAS  Google Scholar 

  • Beauchamp C, Fridovich I (1971) Superoxide dismutase: improved assays and assay applicable to acrylamide gels. Anal Biochem 44:276–286

    Article  CAS  Google Scholar 

  • Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen GM, Green DR (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2:469–475

    Article  CAS  Google Scholar 

  • Brouwer M, Winge DR, Gray WR (1989) Structural and functional diversity of copper- metallothioneins from the American lobster Homarus americanus. J Inorg Biochem 35:289–303

    Article  CAS  Google Scholar 

  • Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  CAS  Google Scholar 

  • Choudhuri S, McKim JM, Klaassen CD (1993) Differential expression of the metallothionein gene in liver and brain of mice and rats. Toxicol Appl Pharmacol 119(1):1–10

    Article  CAS  Google Scholar 

  • Claiborne A (1985) Catalase activity. In: Greenwaid RA (ed) Handbook of methods for oxygen free radical research; CRC Press. Boca Raton, FL

    Google Scholar 

  • Corpas F, Palma PM, Sandalio LM, Lopez-Huertas E, Romero-Puertas MC, Barroso JB (1999) Purification of catalase from pea leaf peroxisomes: identification of five different isoforms. Free Radical Res 31:235–241

    Article  Google Scholar 

  • De Jongh J, DeVito M, Nieboer R, Birnbaum L, Van den Berg M (1995) Induction of cytochrome P450 isoenzymes after toxico-kinetic interactions between 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,2′,4,4′,5,5′-hexachlorobiphenyl in the liver of the mouse. Fund Appl Toxicol 25:264–270

    Article  Google Scholar 

  • Fan GQ, Yuan ZK, Zheng HL, Liu ZJ (2004) Study on the effects of exposure to rare earth elements and health-responses in children aged 7–10 years. J Hyg Res 33:23–28

    Google Scholar 

  • Fei M, Li N, Liu J, Gong XL, Duan YM, Zhao XY, Wang H, Hong FS (2010) Oxidative stress in the liver of mice caused by lanthanoides. Biol Trace Element Res. doi:10.1007/s 12011-010-8638-9

  • Feng ZX, Zhang SG, Yang KY, Ni JZ (1996) Influence of intraperitoneal injection of rare earth compounds on the activity of antioxidant enzymes and the level of lipid peroxidation in mice livers. J Rare Earth 14:66–69

    Google Scholar 

  • Feng JH, Li XJ, Pei FK, Chen X, Li SL, Nie YX (2002) 1H NMR analysis for metabolites in serum and urine from rats administrated chronically with La(NO3)3. Anal Biochem 301:1–7

    Article  CAS  Google Scholar 

  • Feng LX, Xiao HQ, He X, Li ZJ, Li FL, Liu NQ, Chai ZF, Zhao YL, Zhang ZY (2006a) Long-term effects of lanthanum intake on the neurobehavioral development of the rat. Neurotoxicol Teratol 28(1):119–124

    Article  CAS  Google Scholar 

  • Feng LX, Xiao HQ, He X, Li ZJ, Li FL, Liu NQ, Zhao YL, Huang YY, Zhang ZY, Chai ZF (2006b) Neurotoxicological consequence of long-term exposure to lanthanum. Toxicol Lett 165:112–120

    Article  CAS  Google Scholar 

  • Fridovich I (1978) The biology in oxygen radical. Science 201:875–880

    Article  CAS  Google Scholar 

  • Fukuchi K, Tomoyasu S, Tsuruoka N, Gomi K (1994) Iron deprivation-induced apoptosis in HL-60 cells. FEBS Lett 350:139–142

    Article  CAS  Google Scholar 

  • Greisberg JK, Wolf JM, Wyman J, Zou L, Terek RM (2001) Gadolinium inhibits thymidine incorporation and induces apoptosis in chondrocytes. J Orthop Res 19:797–801

    Article  CAS  Google Scholar 

  • Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88

    Article  CAS  Google Scholar 

  • Hissin PJ, Hilf R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74:214–226

    Article  CAS  Google Scholar 

  • Hong HN, Kim HN, Park KS, Lee SK, Gu MB (2007) Analysis of the effects diclofenac has on Japanese medaka (Oryzias latipes) using real-time PCR. Chemosphere 67:2115–2121

    Article  CAS  Google Scholar 

  • Hu Z, Richter H, Sparovek G, Schnug E (2004) Physiological and biochemical effects of rare earth elements on plants and their agricultural significance: a review. J Plant Nutr 27:183–220

    Article  CAS  Google Scholar 

  • Implay JA (2003) Pathways of oxidative damage. Annu Rev Microbiol 57:395–418

    Article  Google Scholar 

  • Jacques-Silva MC, Nogueira CW, Broch LC, Flores EM, Rocha JBT (2001) Diphenyl diselenide and ascorbic changes deposition of selenium and ascorbic in liver and brain of mice. Pharmacol Toxicol 88:119–125

    Article  CAS  Google Scholar 

  • Kawagoe M, Hirasawa F, Wang SC, Liu Y, Ueno Y, Sugiyama T (2005) Orally administrated rare earth element cerium induces metallothionein synthesis and increases glutathione in the mouse liver. Life Sci 77:922–937

    Article  CAS  Google Scholar 

  • Ke LD, Chen Z (2000) A reliability test of standard-based quantitative PCR: exogenous vs endogenous standards. Mol Cell Probes 14(2):127–135

    Article  CAS  Google Scholar 

  • Leaver MJ, Wright J, George SG (1997) Structure and expression of a cluster of glutathione S-transferase genes from a marine fish, the plaice (Pleuronectes platessa). Biochem J 321(Pt 2):405–412

    CAS  Google Scholar 

  • Lewis NA, Williams TD, Chipman JK (2006) Functional analysis of a metal response element in the regulatory region of flounder cytochrome P450 1A and implications for environmental monitoring of pollutants. Toxicol Sci 92:387–393

    Article  CAS  Google Scholar 

  • Li HM, Niki T, Taira T, Iguchi-Ariga SM, Ariga H (2005) Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress. Free Radical Res 39:1091–1099

    Article  CAS  Google Scholar 

  • Li ZF, Wu HF, Zhang XY, Li XJ, Liao PQ, Li WS, Pei FK (2006) Investigation on the acute biochemical effects of light rare earths (lanthanum and cerium) by NMR-based metabonomic approaches. Chem J Chin Univ 27:438–442

    Google Scholar 

  • Liao PQ, Wu HF, Zhang XY, Jing LX, Feng LZ, Sheng LW, Wu YJ, Pei FK (2006) Comparative investigation on acute biological effect of lanthanum and cerium by MAS 1H NMR-based metabonomic approach. Chem J Chin Univ 27:1448–1452

    CAS  Google Scholar 

  • Liao PQ, Zhang XY, Wang T, Sheng LW, Wu YJ, Li XJ, Ni JZ, Pei FK (2008) Studies on the acute biochemical effects of Nd(NO3)3 by nuclear magnetic resonance-based meatbonomics. Chin J Anal Chem 36:426–432

    CAS  Google Scholar 

  • Liu WH, David A (2002) Saint Validation of a quantitative method for real time PCR kinetics. Biochem Biophys Res Commun 294:347–353

    Article  CAS  Google Scholar 

  • Liu HX, Yuan L, Yang XD, Wang K (2003) La3+, Gd3+ and Yb3+ induced changes in mitochondrial structure, membrane permeability, cytochrome c release and intracellular ROS level. Chem-Biol Interact 146:27–37

    Article  CAS  Google Scholar 

  • Liu J, Li N, Ma LL, Duan YM, Wang J, Zhao XY, Hong FS (2010) Mechanism of the splenic injury in mice caused by lanthanides. J Alloys Compounds 489:708–713

    Article  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    CAS  Google Scholar 

  • Marubashi K, Hirano S, Suzuki KT (1998) Effects of intratracheal pretreatment with yttrium chloride (YCl3) on inflammatory responses of the rat lung following intratraccheal instillation of YCl3. Toxicol Lett 99:43–51

    Article  CAS  Google Scholar 

  • Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62:670–684

    Article  CAS  Google Scholar 

  • McKenna IM, Gordon T, Chen LC, Anver MR, Waalkes MP (1998) Expression of metallothionein protein in the lungs of Wistar rats and C57 and DBA mice exposed to cadmium oxide fumes. Toxicol Appl Pharmacol 153(2):169–178

    Article  CAS  Google Scholar 

  • Mizgerd JP, Molina RM, Stearns RC, Brain JD, Warner AE (1996) Gadolinium induces macrophage apoptosis. J Leukoc Biol 59(2):189–195

    CAS  Google Scholar 

  • Ni JZ (2002). Bioinorganic chemistry of rare earth elements. Science Press, Beijing, pp 285–337 (in Chinese)

  • Nourooz-Zadeh J, Tajaddini-Sarmadi J, Wolf SP (1994) Measurement of plasma hydroperoxide concentrations by the ferrous oxidation-xylenol orange assay in conjunction with triphenylphosphine. Anal Biochem 220:403–409

    Article  CAS  Google Scholar 

  • Olafson RW, McCubbin WD, Kay CM (1988) Primary- and secondary-structural analysis of a unique prokaryotic metallothionein from a Synechococcus sp. cyanobacterium. Biochem J 251:691–699

    CAS  Google Scholar 

  • Oliveira CP, Lopasso FP, Laurindo FR, Leitao RM, Laudanna AA (2001) Protection against liver ischemia-reperfusion injury in rats by silymarin or verapamil. Transplant Proc 33:3010–3014

    Article  CAS  Google Scholar 

  • Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    CAS  Google Scholar 

  • Preeta R, Nair RR (1999) Stimulation of cardiac fibroblast proliferation by cerium: a superoxide anion-mediated response. J Mol Cell Cardiol 31:1573–1580

    Article  CAS  Google Scholar 

  • Ren XY, Zhou Y, Zhang JP, Feng WH, Jiao BH (2003) Expression of metallothionein gene at different time in testicular interstitial cells and liver of rats treated with cadmium. World J Gastroentrrol 9(7):1554–1558

    CAS  Google Scholar 

  • Reuveni R, Shimoni M, Karchi Z, Kuc J (1992) Peroxidase activity as a biochemical marker for resistance of muskmelon (Cucumis melo) to seudoperno spora cubensis. Phytopathology 82:749–753

    Article  CAS  Google Scholar 

  • Roesijadi G (1992) Metallothioneins in metal regulation and toxicity in aquatic animals. Aquat Toxicol 22:81–114

    Article  CAS  Google Scholar 

  • Sabbioni E, Pietra R, Gaglione P, Vocaturo G, Colombo F, Zanoni M (1982) Long-term occupational risk of rare earth pneumoconiosis. Sci Total Environ 26:19–32

    Article  CAS  Google Scholar 

  • Shen ZG, Zhang ZX, Huang HX, Zhang JZ, Leng HY, Yang YS (2001) Effect of Ce3+ on reactive oxygen species in cells. J Hyg Res 30:275–277

    CAS  Google Scholar 

  • Shi WL, Shen XY, Ma XY (2006) Effects of samarium on liver and kidney of rats. J Rare Earth 24:415–448

    Article  Google Scholar 

  • Truksa J, Kovar J, Valenta T, Ehrlichova M, Polak J, Naumann PW (2003) Iron deprivation induces apoptosis independently of p53 in human and murine tumour cells. Cell Prolif 36:199–213

    Article  CAS  Google Scholar 

  • Wahba ZZ (1994) Absence of changes in metallothionein RNA in the rat testes made refractory to cadmium toxicity by zinc pretreatment. Hum Exp Toxicol 13(1):65–67

    Article  CAS  Google Scholar 

  • Wang K, Li RC, Cheng Y, Zhu B (1999) Lanthanides—the future drugs? Coord Chem Rev 190:297–308

    Article  Google Scholar 

  • Welch S (1992) Transferrin: the iron carrier. CRC Press, Boca Raton, FL

    Google Scholar 

  • Wu HF, Zhang XY, Li XJ, Wu YJ, Pei FK (2005) Acute biochemical effects of La(NO3)3 on liver and kidney tissues by magic-angle spinning 1H nuclear magnetic resonance spectroscopy and pattern recognition. Anal Biochem 339:242–248

    Article  CAS  Google Scholar 

  • Xia Q, Chen D, Liu YR, Chen AJ (2006) Effect of mixed rare earth oxide “changle” on rat liver. Chin Rare Earth 27:76–78 (abstract in English)

    Google Scholar 

  • Xu X, Zhu W, Wang Z, Witkamp GJ (2002) Distribution of rare earths and heavy metals in field-grown maize after application of rare earth-containing fertilizers. Sci Total Environ 293:97–105

    Article  CAS  Google Scholar 

  • Zhang S, Shan X (2001) Speciation of rare earth elements in soil and accumulation by wheat with rare earth fertilizer application. Environ Pollut 112:395–405

    Article  CAS  Google Scholar 

  • Zhang H, Feng J, Zhu WF (1999) Characteristic of rare earth distribution in biologic chains of rare earth-rich background regions. J Chin Rare Earth Soc 174(4):365–368

    Google Scholar 

  • Zhang YL, Zhang X, Fei XC, Wang SL, Ga HW (2010) Binding of bisphenol A and acrylamide to BSA and DNA: insights into the comparative interactions of harmful chemicals with functional biomacromolecules. J Hazard Mater 182:877–885

    Article  CAS  Google Scholar 

  • Zhu WF, Xu SQ, Zhang H, Shao PP, Wu DS, Yang WJ, Feng J (1996) Investigation of children intelligence quotient in REE mining area: bio-effect study of REE mining area in South Jiangxi. Chin Sci Bull 41:914–916

    Google Scholar 

  • Zhu WF, Xu SQ, Shao PP, Zhang H, Wu DS, Yang WJ, Feng J (1997) Bioelectrical activity of the central nervous system among populations in a rare earth element area. Biol Trace Element Res 57:71–77

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant No. 30901218), the “Chun-Tsung scholar” Foundation of Soochow University, and the New Ideas Foundation of Student of Soochow University (grant No. 5731511410).

Author information

Authors and Affiliations

  1. Medical College of Soochow University, Suzhou, 215123, People’s Republic of China

    Haiquan Zhao, Jie Cheng, Jingwei Cai, Zhe Cheng, Yaling Cui, Guodong Gao, Renping Hu, Xiaolan Gong, Ling Wang & Fashui Hong

  2. College of Life Sciences, Anhui Agriculture University, Hefei, 230036, People’s Republic of China

    Haiquan Zhao

Authors
  1. Haiquan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jingwei Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhe Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yaling Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guodong Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Renping Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaolan Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ling Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fashui Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fashui Hong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, H., Cheng, J., Cai, J. et al. Liver Injury and Its Molecular Mechanisms in Mice Caused by Exposure to Cerium Chloride. Arch Environ Contam Toxicol 62, 154–164 (2012). https://doi.org/10.1007/s00244-011-9672-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00244-011-9672-0

Keywords

Search

Navigation