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Effects of α-tocopherol on serum trace and major elements in rats with bleomycin-induced pulmonary fibrosis


The study was undertaken to investigate the influence of α-tocopherol on zinc, copper, iron, calcium, magnesium, and potassium concentrations in serum of rats with bleomycin-induced pulmonary fibrosis. Fourteen Wistar albino rats were randomly divided into two groups of seven animals each. The first group was treated intratracheally with bleomycin hydrochloride (BM group); the second group was also instilled with BM but received injections of α-tocopherol twice a week (BM+E group). The third group was treated in the same manner with saline solution only, acting as controls (C). The zinc concentrations of the BM and BM+E groups were significantly decreased compared to the controls (p<0.05). The iron concentration of the controls was significantly higher than the other two groups. The magnesium concentration in the controls and the BM+E group was significantly higher than that of the BM group. The serum copper, calcium, and potassium concentrations were not found to be statistically different among the three groups. Distinct histopathologic changes were found in the BM group compared to the untreated rats. Less severe fibrotic lesions were also observed in the BM+E group. The results of this study show that lungs of rats treated with bleomycin were seriously damaged and that vitamin E seemed to counteract some of the damage, as indicated by differences in the serum concentrations of major elements.

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  1. 1.

    F. S. Tadzhiev, L. N. Danilov, E. S. Lebedeva, N. A. Panichev, and M. Sou, Content of trace elements and steroid hormones in blood and tissues of internal organs in experimental pulmonary fibrosis induced by intratracheal administration of bleomycetin, Fiziol. Eksp. Ter. 3, 5–7 (1992).

    Google Scholar 

  2. 2.

    Z. E. Suntres and P. N. Shek, Protective effect of liposomal alpha-tocopherol against bleomycin-induced lung injury, Biomed. Environ. Sci. 10(1), 47–59 (1997).

    PubMed  CAS  Google Scholar 

  3. 3.

    C. Kilinc, O. Ozcan, E. Karaoz, K. Sunguroglu, T. Kutluay, and L. Karaca, Vitamin E reduces bleomycin-induced lung fibrosis in mice: biochemical and morphological studies, Basic. Clin. Physiol. Pharmacol. 4(3), 249–269 (1993).

    CAS  Google Scholar 

  4. 4.

    F. Villani, M. Galimberti, A. Barbieri, M. Luisetti, L. Bacchella, and C. Aprile, Biochemical and functional markers of lung damage after bleomycin treatment, Monaldi Arch. Chest Dis. 50(3), 183–186 (1995).

    PubMed  CAS  Google Scholar 

  5. 5.

    A. E. Huot, R. M. Gundel, and M. P. Hacker, Effect of erythrocytes on alveolar macrophage cytostatic activity induced by bleomycin lung damage in rats, Cancer Res. 50(8), 2351–2355 (1990).

    PubMed  CAS  Google Scholar 

  6. 6.

    H. Ozyurt, S. Sogut, Z. Yildirim, et al. Inhibitory effect of caffeic acid phenethyl ester on bleomycine-induced lung fibrosis in rats, Clin. Chim. Acta 339(1–2), 65–75 (2004).

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    D. B. Chandler, J. C. Barton, D. D. Briggs, et al., Effects of iron deficiency on bleomycin-induced lung fibrosis in the hamster, Am. Rev. Respir. Dis. 137(1), 85–89 (1988).

    PubMed  CAS  Google Scholar 

  8. 8.

    K. Takahashi, Pulmonary fibrosis and antioxidant agents, Nih. Kyo. Shik Gak Zas 27(4), 428–433 (1989).

    CAS  Google Scholar 

  9. 9.

    I. Fridovich, Superoxide radical and superoxide dismutases, Annu. Rev. Biochem. 64, 97–112 (1995).

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    L. Costanzo, D. Guidi, S. Giuffrida, S. Sortino, and G. Condorelli, Antioxidant effect of inorganic ions on UVC and UVB induced lipid peroxidationm, J. Inorg. Biochem. 59(1), 1–13 (1995).

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    R. W. Byrnes and D. H. Petering, DNA strand breakage in isolated nuclei subjected to bleomycin or hydrogen peroxide, Biochem. Pharmacol. 48, 575–582 (1994).

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    J. M. Gutteridge and Y. Y. Hou, Iron complexes and their reactivity in the bleomycin assay for radical-promoting loosely-bound iron, Free Radical Res. Commun. 2(3), 143–151 (1986).

    CAS  Google Scholar 

  13. 13.

    A. E. Filderman, L. A. Genovese, and J. S. Lazo, Alterations in pulmonary protective enzymes following systemic bleomycin treatment in mice, Biochem. Pharmacol. 37, 1111–1116 (1988).

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    T. D. Oury, K. Thakker, M. Menache, L. Y. Changg, J. D. Crapo, and J. D. Day, Attenuation of bleomycin-induced pulmonary fibrosis by catalytic antioxidant metalloporphyrin, Am. J. Respir. Crit. Care Med. 164, 164–169 (2001).

    Google Scholar 

  15. 15.

    L. G. Wood, P. G. Gibson and M. L. Garg, Circulating markers to assess nutritional therapy in cystic fibrosis, Clin. Chim. Acta 353(1–2), 13–29 (2005).

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    E. J. Underwood, Trace Elements in Human and Animal Nutrition, Academic, New York (1977).

    Google Scholar 

  17. 17.

    L. H. Schwartz, T. Urban, and S. Herzberg, Antioxidant minerals and vitamins. Role in cancer prevention, Press. Med. 23(39), 1826–1830 (1994).

    CAS  Google Scholar 

  18. 18.

    J. F. Weiss and M. R. Landauer, Radioprotection by antioxidants, Ann. NY Acad. Sci. 899, 44–60 (2000).

    PubMed  CAS  Article  Google Scholar 

  19. 19.

    B. M. Winklhofer-Roob, E. Rock, J. Ribalta, D. H. Shmerling, and J. M. Roob, Effects of vitamin E and carotenoid status on oxidative stress in health and disease. Evidence obtained from human intervention studies. Mol. Aspects Med. 24(6), 391–402 (2003).

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    A. Molteni, B. L. Herndon, A. Kamal, et al., Effect of the antioxidant α-tocopherol in an experimental model of pulmonary hypertension and fibrosis: administration of monocrotaline, Nutr. Res. 24, 707–720 (2004).

    Article  CAS  Google Scholar 

  21. 21.

    K. Woniak, M. Arabski, E. Macka-Panas, J. Drzewoski, and J. Basiak, DNA damage in human colonic mucosa cells induced by bleomycin and the protective action of Vit E, Cell. Mol. Biol. Lett. 79, 31–45 (2004).

    Google Scholar 

  22. 22.

    S. A. Peters and F. J. Kelly, Vitamin E supplementation in cystic fibrosis, J. Pediatr. Gastroenterol. Nutr. 22(4), 341–345 (1996).

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    J. D. Bancroff and H. J. Cook, Mammal of Histological Tecniques, Churchill Livingstone, New York (1984).

    Google Scholar 

  24. 24.

    W. E. Greenberg, R. R. Trusell, and L. S. Clescer, Standard Methods for the Examination of Water and Wastewater, 60th ed., American Public Health Association, Washington, DC (1996).

    Google Scholar 

  25. 25.

    J. E. Longbottom, T. D. Martin, K. W. Edgell, S. E. Long, M. R. Plantz, and B. E. Warden, Determination of trace elements in water by inductively coupled plasma-mass spectrometry: collaborative study, JAOAC Int. 77(4), 1004–1023 (1994).

    CAS  Google Scholar 

  26. 26.

    S. N. Giri, R. Blaisdell, R. B. Rucker, Q. Wang, and D. M. Hyde, Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms, Environ. Health Perspect. 102 (Suppl. 10), 137–147 (1994).

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    J. W. Card, R. G. Leeder, W. J. Racz, J. F. Brien, T. M. Bray, and T. E. Massey, Effects of dietary vitamin E supplementation on pulmonary morphology and collagen deposition in amiodarone-and vehicle-treated hamsters, Toxicology 133(2–3), 75–84 (1999).

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    M. Zowczak, M. Iskra, L. Torlinski, and S. Cofta, Analysis of serum copper and zinc concentrations in cancer patients, Biol. Trace Element Res. 82(1–3), 1–8 (2001).

    Article  CAS  Google Scholar 

  29. 29.

    J. Neve, R. van Geffel, M. Hanocq, and L. Molle, Plasma and erythrocyte zinc, copper and selenium in cystic fibrosis, Acta Paediatr. Scand. 72, 437–440 (1983).

    PubMed  CAS  Google Scholar 

  30. 30.

    F. S. Tadzhiev, A. N. Kokosov, M. M. Il'kovich, and N. V. Syromiatnikova, Steroid hormone and trace element content of the blood in patients with disseminated processes of the lungs, Probl. Tuberk. 11, 6–9 (1989).

    PubMed  Google Scholar 

  31. 31.

    W. F. Ward, A. Molteni, C. Ts'ao, and H. Ischiropoulos, Serum copper concentration as an index of experimental lung injury, Adv. Exp. Med. Biol. 258, 287–302 (1989).

    PubMed  CAS  Google Scholar 

  32. 32.

    G. J. Brewer, M. R. Ullenbruch, R. Dick, L. Olivarez, and S. H. Phan, Tetrathiomolybdate therapy protects against bleomycin-induced pulmonary fibrosis in mice, J. Lab. Clin. Med. 141(3), 210–216 (2003).

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    D. R. Richardson, Analogues of pyridoxal isonicotinoyl hydrazone (PIH) as potential iron chelators for the treatment of neoplasia, Leuk. Lymphoma 31(1–2), 47–60 (1998).

    PubMed  CAS  Google Scholar 

  34. 34.

    M. L. Plit, A. J. Theron, H. Fickl, C. E. van Rensburg, S. Pendel, and R. Anderson, Influence of antimicrobial chemotherapy and smoking status on the plasma concentrations of vitamin C, vitamin E, beta-carotene, acute phase reactants, iron and lipid peroxides in patients with pulmonary tuberculosis, Int. J. Tuberc. Lung Dis. 2(7), 590–596 (1998).

    PubMed  CAS  Google Scholar 

  35. 35.

    J. M. Nakashima, D. M. Hyde, and S. N. Giri, Effects of a calmodulin inhibitor on bleomycin-induced lung inflammation in hamsters. Biochemical, morphometric, and bronchoalveolar lavage data, Am. J. Pathol. 124(3), 528–536 (1986).

    PubMed  CAS  Google Scholar 

  36. 36.

    S. G. Wannamethee, A. F. Lever, A. G. Shaper, and P. H. Whincup, Serum potassium, cigarette smoking, and mortality in middle-aged men, Am. J. Epidemiol. 145(7), 598–606 (1997).

    PubMed  CAS  Google Scholar 

  37. 37.

    I. T. Piatnochka and V. Z. Sikora, Chemical elements in the blood, bronchial lavage fluid and lung tissue of patients with pulmonary tuberculosis and lung cancer, Probl. Tuberk. 7, 35–37 (1991).

    PubMed  Google Scholar 

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Correspondence to Semiha Dede.

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Dede, S., Mert, H., Mert, N. et al. Effects of α-tocopherol on serum trace and major elements in rats with bleomycin-induced pulmonary fibrosis. Biol Trace Elem Res 114, 175–184 (2006).

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Index Entries

  • Bleomycin
  • macroelements
  • pulmonary fibrosis
  • serum
  • trace elements