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Reversal of aminopterin toxicity by water-soluble cupridihydroporphyrins (Chloresium)

  • Robert D. Barnard
  • Mark D. Freeman
Original contribution

Summary

Ingestion of 2 mg. per kilo per day of water-soluble cupri-chlorophyllins (Chloresium) protected weanling rats on a milk diet from aminopterin toxicity in each of seven experimental series. Similar protection was observed in one series of rats on a standard laboratory diet and in one series on laboratory diet supplemented with fresh greens.

In a single screening series, some protection of aminopterin-poisoned rats on a milk diet was forthcoming from administration of terramycin at 2 mg. per kilo per day, from Renshaw’s mammalian intestinal mucosa extract and from the parenteral administration of human plasma cholinesterase. Coprogen did not prolong survival under present experimental conditions. Availability of iron for hemoglobin synthesis from ferri-dihydroporphyrin (ferri-chlorophyllin) where the iron is chelated, in aminopterin-poisoned weanling rats on a milk diet, was not demonstrated.

The mechanism of chlorophyllin abrogation of aminopterin toxicity is analyzed. It is concluded that this does not result from chemical inactivation of aminopterin in vitro or in vivo. It may act as a formyl donor. However, chlorophyllin may also act by reversion of the fecal flora of ingesting animals in the same way as do other APF substances (mycin antibiotics, 11-oxysteroids and unidentified factors found in streptomyces fermentation residues).

The findings are presented because of the serious toxicity limitations of folic-acids in neoplastic disease. While their clinical use is probably on the wane, as long as they are so used, any knowledge of their counteraction is of clinical interest.

Keywords

Acute Leukemia Chlorophyllin Terramycin Aureomycin Kwashiorkor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Reefeeences

  1. 1.
    Barnard, R. D.: Folic Acid in Acute Leukemia, Canad. M.A.J.,63:614, (Dec.) 1950.Google Scholar
  2. 2.
    Bennette, J. G.: Amethopterin—A Toxic Tumor Inhibitor, Brit. J. Cancer6:377, 1952.PubMedGoogle Scholar
  3. 3.
    Totter, J. R.: Personal communication.Google Scholar
  4. 4.
    Boyd, E. M. and Delahaye, J. K.: Neutralization of Aminopterin-Induced Leucopenia by Adenosine 5 Phosphate, J. Lab. and Clin. Med.41:931, 1953.Google Scholar
  5. 5.
    Waisman, H. A., Green, M., Cravioto-Munoz, J., Ramenchik, A., and Richmond, J. B.: Role of Aureomycin and Citrovorum Factor in “Folie Acid” Deficiencies, Proc. Soc. Exp. Biol. and Med.76:384, 1951.Google Scholar
  6. 6.
    Sauberlich, H. E.: Studies on the Eeversal of Aminopterin Toxicity in the Eat with Citrovorum. Factor, Folacin and Belated Compounds, J. Nutrition50:101, (May) 1953.Google Scholar
  7. 7.
    Barnard, R. D.: Unpublished data.Google Scholar
  8. 8.
    Ritter, H. B., Oleson, J. J., Hutchins, B. L. and Williams, J. H.: The Erythropoietic Activity of Coprogen, Arch. Biochem.42:475, (Feb.) 1953.PubMedCrossRefGoogle Scholar
  9. 9.
    Alles, G. A. and Hawes, R. C.: Cholintsterase in the Blood of Man, J. Biol. Chem.46:184, 1940.Google Scholar
  10. 10.
    Renshaw, A. R.: Functional Role of Intestinal Mueosa in Eheumatic Disease, Ann. Rheum. Dis.6:15, 1947.CrossRefPubMedGoogle Scholar
  11. 11.
    Tove, C. B., Lalor, R. J. and Elvehjem, C. A.: An Unidentified Factor Present in Hog Intestinal Mueosa Required by the Mink, J. Nutrition42:431, 1950.Google Scholar
  12. 12.
    Tomarelli, R. M., Norris, R. F., Rose, C. S. and Gyorgy, P.: Effect of Fatty Acids on Growth of Strains of Laetobacillus Bifidus, J. Biol. Chem.87:197, 1950.Google Scholar
  13. 13.
    Scott, E. and Delor, C. J.: Effect of Alfalfa Extract on Iron-Copper Deficiency Anemia in Rats, Ohio State M. J.29:165, 1933.Google Scholar
  14. 14.
    Schwarz, K.: Effect of Aureomycin on Folic Acid-Citrovorum Factor Relation in the Rat, Fed. Proc.10:394, (Mar.) 1951.Google Scholar
  15. 15.
    Barnard, R. D. and Fox, H. L.: Innoeuity of Protracted Administration of Crude B12-Containing Fermentation Concentrates as Demonstrated in a Patient with Acute Leukemia, Ohio State M. J., 46:784 (Aug.) 1950.Google Scholar
  16. 16.
    Goldman, B.: Personal communication.Google Scholar
  17. 17.
    Marks, M. M.: Streptomyces-Antibiotic Residues in Ulcerative Colitis, Paper presented before AMA convention, N. Y. City, June 11, 1953.Google Scholar

Copyright information

© Sandfield Publishing Company 1954

Authors and Affiliations

  • Robert D. Barnard
    • 1
  • Mark D. Freeman
    • 1
  1. 1.Pharmacology Section of the Laboratory Research DivisionRystan CompanyMount Vernon

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