Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1990 Sep;34(9):1833–1835. doi: 10.1128/aac.34.9.1833

Deferoxamine and eflornithine (DL-alpha-difluoromethylornithine) in a rat model of Pneumocystis carinii pneumonia.

A B Clarkson Jr 1, M Sarić 1, R W Grady 1
PMCID: PMC171942  PMID: 2285303

Abstract

The iron chelator deferoxamine and the polyamine biosynthesis inhibitor eflornithine (DL-alpha-difluoromethylornithine) were examined for anti-Pneumocystis carinii activity in the rat model of P. carinii pneumonia. The activity of deferoxamine at 250, 500, and 1,000 mg/kg given intraperitoneally provides evidence that iron chelation is a promising novel approach to P. carinii chemotherapy. Results with eflornithine at 2, 3, and 4% in drinking water confirm and extend previously reported activity in the rat model.

Full text

PDF
1833

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aldouri M. A., Wonke B., Hoffbrand A. V., Flynn D. M., Laulicht M., Fenton L. A., Scheuer P. J., Kibbler C. C., Allwood C. A., Brown D. Iron state and hepatic disease in patients with thalassaemia major, treated with long term subcutaneous desferrioxamine. J Clin Pathol. 1987 Nov;40(11):1353–1359. doi: 10.1136/jcp.40.11.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bowling M. C., Smith I. M., Wescott S. L. A rapid staining procedure for Pneumocystis carinii. Am J Med Technol. 1973 Jul;39(7):267–268. [PubMed] [Google Scholar]
  3. Clarkson A. B., Jr, Williams D. E., Rosenberg C. Efficacy of DL-alpha-difluoromethylornithine in a rat model of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1988 Aug;32(8):1158–1163. doi: 10.1128/aac.32.8.1158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Edman J. C., Kovacs J. A., Masur H., Santi D. V., Elwood H. J., Sogin M. L. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature. 1988 Aug 11;334(6182):519–522. doi: 10.1038/334519a0. [DOI] [PubMed] [Google Scholar]
  5. Engelberg L. A., Lerner C. W., Tapper M. L. Clinical features of Pneumocystis pneumonia in the acquired immune deficiency syndrome. Am Rev Respir Dis. 1984 Oct;130(4):689–694. doi: 10.1164/arrd.1984.130.4.689. [DOI] [PubMed] [Google Scholar]
  6. Fritsch G., Treumer J., Spira D. T., Jung A. Plasmodium vinckei: suppression of mouse infections with desferrioxamine B. Exp Parasitol. 1985 Oct;60(2):171–174. doi: 10.1016/0014-4894(85)90020-7. [DOI] [PubMed] [Google Scholar]
  7. Haverkos H. W. Assessment of therapy for pneumocystis carinii pneumonia. PCP Therapy Project Group. Am J Med. 1984 Mar;76(3):501–508. doi: 10.1016/0002-9343(84)90670-3. [DOI] [PubMed] [Google Scholar]
  8. Heppner D. G., Hallaway P. E., Kontoghiorghes G. J., Eaton J. W. Antimalarial properties of orally active iron chelators. Blood. 1988 Jul;72(1):358–361. [PubMed] [Google Scholar]
  9. Hopewell P. C., Luce J. M. Pulmonary involvement in the acquired immunodeficiency syndrome. Chest. 1985 Jan;87(1):104–112. doi: 10.1378/chest.87.1.104. [DOI] [PubMed] [Google Scholar]
  10. Hughes W. T., Smith B. L. Efficacy of diaminodiphenylsulfone and other drugs in murine Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother. 1984 Oct;26(4):436–440. doi: 10.1128/aac.26.4.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kouides P. A., Slapak C. A., Rosenwasser L. J., Miller K. B. Pneumocystis carinii pneumonia as a complication of desferrioxamine therapy. Br J Haematol. 1988 Nov;70(3):383–384. doi: 10.1111/j.1365-2141.1988.tb02500.x. [DOI] [PubMed] [Google Scholar]
  12. Leggiadro R. J., Winkelstein J. A., Hughes W. T. Prevalence of Pneumocystis carinii pneumonitis in severe combined immunodeficiency. J Pediatr. 1981 Jul;99(1):96–98. doi: 10.1016/s0022-3476(81)80967-5. [DOI] [PubMed] [Google Scholar]
  13. Matsumoto Y., Matsuda S., Tegoshi T. Yeast glucan in the cyst wall of Pneumocystis carinii. J Protozool. 1989 Jan-Feb;36(1):21S–22S. doi: 10.1111/j.1550-7408.1989.tb02674.x. [DOI] [PubMed] [Google Scholar]
  14. Maurer H. S., Lloyd-Still J. D., Ingrisano C., Gonzalez-Crussi F., Honig G. R. A prospective evaluation of iron chelation therapy in children with severe beta-thalassemia. A six-year study. Am J Dis Child. 1988 Mar;142(3):287–292. doi: 10.1001/archpedi.1988.02150030057020. [DOI] [PubMed] [Google Scholar]
  15. Mitsuyasu R., Groopman J., Volberding P. Cutaneous reaction to trimethoprim-sulfamethoxazole in patients with AIDS and Kaposi's sarcoma. N Engl J Med. 1983 Jun 23;308(25):1535–1536. doi: 10.1056/NEJM198306233082512. [DOI] [PubMed] [Google Scholar]
  16. Pesanti E. L., Bartlett M. S., Smith J. W. Lack of detectable activity of ornithine decarboxylase in Pneumocystis carinii. J Infect Dis. 1988 Nov;158(5):1137–1138. doi: 10.1093/infdis/158.5.1137. [DOI] [PubMed] [Google Scholar]
  17. Peto T. E., Thompson J. L. A reappraisal of the effects of iron and desferrioxamine on the growth of Plasmodium falciparum 'in vitro': the unimportance of serum iron. Br J Haematol. 1986 Jun;63(2):273–280. doi: 10.1111/j.1365-2141.1986.tb05550.x. [DOI] [PubMed] [Google Scholar]
  18. Pollack S., Rossan R. N., Davidson D. E., Escajadillo A. Desferrioxamine suppresses Plasmodium falciparum in Aotus monkeys. Proc Soc Exp Biol Med. 1987 Feb;184(2):162–164. doi: 10.3181/00379727-184-42461. [DOI] [PubMed] [Google Scholar]
  19. Propper R., Nathan D. Clinical removal of iron. Annu Rev Med. 1982;33:509–519. doi: 10.1146/annurev.me.33.020182.002453. [DOI] [PubMed] [Google Scholar]
  20. Raventos-Suarez C., Pollack S., Nagel R. L. Plasmodium falciparum: inhibition of in vitro growth by desferrioxamine. Am J Trop Med Hyg. 1982 Sep;31(5):919–922. doi: 10.4269/ajtmh.1982.31.919. [DOI] [PubMed] [Google Scholar]
  21. Siegel S. E., Wolff L. J., Baehner R. L., Hammond D. Treatment of Pneumocystis carinii pneumonitis. A comparative trial of sulfamethoxazole-trimethoprim v pentamidine in pediatric patients with cancer: report from the Children's Cancer Study Group. Am J Dis Child. 1984 Nov;138(11):1051–1054. [PubMed] [Google Scholar]
  22. Sjoerdsma A. Suicide enzyme inhibitors as potential drugs. Clin Pharmacol Ther. 1981 Jul;30(1):3–22. doi: 10.1038/clpt.1981.121. [DOI] [PubMed] [Google Scholar]
  23. Summers M. R., Jacobs A., Tudway D., Perera P., Ricketts C. Studies in desferrioxamine and ferrioxamine metabolism in normal and iron-loaded subjects. Br J Haematol. 1979 Aug;42(4):547–555. doi: 10.1111/j.1365-2141.1979.tb01167.x. [DOI] [PubMed] [Google Scholar]
  24. Walzer P. D., Kim C. K., Foy J., Linke M. J., Cushion M. T. Cationic antitrypanosomal and other antimicrobial agents in the therapy of experimental Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1988 Jun;32(6):896–905. doi: 10.1128/aac.32.6.896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Winston D. J., Lau W. K., Gale R. P., Young L. S. Trimethoprim-sulfamethoxazole for the treatment of Pneumocystis carinii pneumonia. Ann Intern Med. 1980 Jun;92(6):762–769. doi: 10.7326/0003-4819-92-6-762. [DOI] [PubMed] [Google Scholar]
  26. Yinnon A. M., Theanacho E. N., Grady R. W., Spira D. T., Hershko C. Antimalarial effect of HBED and other phenolic and catecholic iron chelators. Blood. 1989 Nov 1;74(6):2166–2171. [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES