Archives of Toxicology

, Volume 81, Issue 6, pp 389–395 | Cite as

Uranium induces oxidative stress in lung epithelial cells

  • Adaikkappan  Periyakaruppan
  • Felix Kumar
  • Shubhashish  Sarkar
  • Chidananda S. Sharma
  • Govindarajan T.  RameshEmail author
Inorganic Compounds


Uranium compounds are widely used in the nuclear fuel cycle, antitank weapons, tank armor, and also as a pigment to color ceramics and glass. Effective management of waste uranium compounds is necessary to prevent exposure to avoid adverse health effects on the population. Health risks associated with uranium exposure includes kidney disease and respiratory disorders. In addition, several published results have shown uranium or depleted uranium causes DNA damage, mutagenicity, cancer and neurological defects. In the current study, uranium toxicity was evaluated in rat lung epithelial cells. The study shows uranium induces significant oxidative stress in rat lung epithelial cells followed by concomitant decrease in the antioxidant potential of the cells. Treatment with uranium to rat lung epithelial cells also decreased cell proliferation after 72 h in culture. The decrease in cell proliferation was attributed to loss of total glutathione and superoxide dismutase in the presence of uranium. Thus the results indicate the ineffectiveness of antioxidant system’s response to the oxidative stress induced by uranium in the cells.


Uranium Glutathione Reactive oxygen species Superoxide dismutase Cell proliferation Lipid hydroperoxide 



This work was supported by NASA funding NCC 9-165: NCC-1-02038: NAG 9-1414: NIH/RCMI RR03045-19 (GR).


  1. Ahlemeyer B, Bauerbach E, Plath M, Steuber M, Heers C, Tegtmeier F, Krieglstein J (2001) Retinoic acid reduces apoptosis and oxidative stress by preservation of SOD protein level. Free Radic Biol Med 30:1067–1077PubMedCrossRefGoogle Scholar
  2. Albina ML, Belles M, Gomez M, Sanchez DJ, Domingo JL (2003) Influence of maternal stress on uranium-induced developmental toxicity in rats. Exp Biol Med 228:1072–1077Google Scholar
  3. Bruske-Hohlfeld I, Rosario AS, Wolke G, Heinrich J, Kreuzer M, Kreienbrock L, Wichmann HE (2006) Lung cancer risk among former uranium miners of the WISMUT company in Germany. Health Phys 90:208–216PubMedCrossRefGoogle Scholar
  4. Coryell VH, Stearns DM (2006) Molecular analysis of hprt mutations generated in Chinese hamster ovary EM9 cells by uranyl acetate, by hydrogen peroxide, and spontaneously. Mol Carcinog 45:60–72PubMedCrossRefGoogle Scholar
  5. Dick CAJ, Brown DM, Donaldson K, StoneV (2003) The role of free radicals in the toxic and inflammatory affects of four different ultrafine particle types. Inhal Toxicol 1:39–52CrossRefGoogle Scholar
  6. Domej W, Foldes-Papp Z, Flogel E, Haditsch B (2006) Chronic obstructive pulmonary disease and oxidative stress. Curr Pharm Biotechnol 7:117–1123PubMedCrossRefGoogle Scholar
  7. Filomeni G, Ciriolo MR (2006) Redox control of apoptosis: an update. Antioxid Redox Signal 8:2187–2192PubMedCrossRefGoogle Scholar
  8. Gazin V, Kerdine S, Grillon G, Pallardy M, Raoul H (2004) Uranium induces TNF—α secretion and MAPK activation in a rat alveolar macrophage cell line. Toxicol Appl Pharmacol 1:49–59CrossRefGoogle Scholar
  9. Hussain S, Rodgers DA, Duhart HM, Ali SF (1977) Mercuric chloride-induced reactive oxygen species and its effect on antioxidant enzymes in different regions of rat brain. J Environ Sci Health 32:395–409Google Scholar
  10. Kalinich JF, Ramakrishnan N, Villa V, McClain DE (2002) Depleted uranium—uranyl chloride induces apoptosis in mouse J774 macrophages. Toxicology 179:105–114PubMedCrossRefGoogle Scholar
  11. Kryscio A, Ulrich Muller WU, Wojcik A, Kotschy N, Grobelny S, Streffer C (2001) A cytogenetic analysis of the long—term effect of uranium mining on peripheral lymphocytes using the micronucleus-centromere assay. Int J Radiat Biol 77:1087–1093PubMedCrossRefGoogle Scholar
  12. Malard V, Prat O, Darrouzet E, Berenguer F, Sage N, Quemeneur E (2005) Proteomic analysis of the response of human lung cells to uranium. Proteomics 5:4568–4580PubMedCrossRefGoogle Scholar
  13. Manna SK, Sarkar S, Barr J, Wise K, Barrera EV, Jejelowo O, Rice- Ficht AC, Ramesh GT (2005) Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-kappaB in human keratinocytes. NanoLetters 5:1676–1684Google Scholar
  14. Meister A (1994) Glutathione, ascorbate, and cellular protection. Cancer Res 54:1969–1975Google Scholar
  15. Monleau M, De-Meo M, Paquet F, Chazel V, Dumenil G, Donnadieu- Claraz M (2006) Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats. Toxiol Sci 89:287–295CrossRefGoogle Scholar
  16. Prat O, Berenguer F, Malard V, Tavan E, Sage N, Steinmetz G, Quemeneur E (2005) Transcriptomic and proteomic responses of human renal HEK293 cells to uranium toxicity. Proteomics 5:297–306PubMedCrossRefGoogle Scholar
  17. Rahman I, Biswas SK, Kode A (2006) Oxidant & antioxidant balance in the airways and airway diseases. Eur J Pharmacol 533:222–239PubMedCrossRefGoogle Scholar
  18. Sanchez DJ, Belles M, Albina ML, Sirvent JJ, Domingo J L (2001) Nephrotoxicity of simultaneous exposure to mercury and uranium in comparison to individual effects of these metals in rats. Biol Trace Elem Res 84:139–154PubMedCrossRefGoogle Scholar
  19. Sarkar S, Sharma C, Periyakaruppan A, Jejelowo O, Thomas R, Barrera EV, Rice-Ficht AC, Wilson BL, Ramesh GT (2006) Analysis of stress responsive genes induced by single walled carbon nanotubes in BJ Foreskin cells. J Nanosci Nanotechnol (in press)Google Scholar
  20. Sharma CS, Sarkar S, Periyakaruppan A, Barr J, Wise K, Thomas R, Wilson BL, Ramesh GT (2006) Single walled carbon nanotubes induces oxidative stress in rat lung epithelial cell. J Nanosci Nanotechnol (in press)Google Scholar
  21. Stearns DM, Yazzie M, Bradley AS, Coryell VH, Shelley JT, Ashby A, Asplund CS, Lantz RC (2005) Uranyl acetate induces hprt mutations and uranium–DNA adducts in Chinese hamster ovary EM 9 cells. Mutagenesis 20:417–423PubMedCrossRefGoogle Scholar
  22. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40PubMedCrossRefGoogle Scholar
  23. Wise KC, Manna SK, Yamauchi K, Ramesh V, Wilson BL, Thomas RL, Sarkar S, Kulkarni AD, Pellis NR, Ramesh GT (2005) Activation of nuclear transcription factor–kappa B in mouse brain induced by a simulated microgravity environment. In Vitro Cell Dev Biol Anim 41:118–123PubMedCrossRefGoogle Scholar
  24. Yadav P, Bhatnagar D, Sarkar S (1994) Counteraction of glutathione and selenium of the proxidant effect of alloxan in erythrocytes in vitro. Toxicol In Vitr 8:1259–1263CrossRefGoogle Scholar
  25. Yao EH, Yu Y, Fukuda N (2006) Oxidative stress on progenitor and stem cells in cardiovascular diseases. Curr Pharm Biotechnol 2:101–108CrossRefGoogle Scholar
  26. Yazzie M, Gamble SL, Civitello ER, Stearns DM (2003) Uranyl acetate causes DNA single strand breaks in vitro in the presence of ascorbate (vitamin C). Chem Res Toxicol 16:524–530PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Adaikkappan  Periyakaruppan
    • 1
  • Felix Kumar
    • 1
  • Shubhashish  Sarkar
    • 1
  • Chidananda S. Sharma
    • 1
  • Govindarajan T.  Ramesh
    • 1
    Email author
  1. 1.Molecular Neurotoxicology Laboratory/Proteomics Core, Department of BiologyTexas Southern UniversityHoustonUSA

Personalised recommendations