QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Peterson, F. J. Articles by Mason, R. P. Search for Related Content PubMed PubMed Citation Articles by Peterson, F. J. Articles by Mason, R. P.

Effect of Selenium and Vitamin E Deficiency on Nitrofurantoin Toxicity in the Chick¹

Francis J. Peterson^2,*,,, Gerald F. Combs, Jr., Jordan L. Holtzman^*,, and Ronald P. Mason^3,*

^* Research Service, Veterans Administration Medical Center, Minneapolis, MN 55417; Departments of Medicine and Pharmacology, University of Minnesota, Minneapolis, MN 55417 Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853

The acute toxicity of nitrofurantoin was studied in the young chick deficient in selenium (Se) and/or vitamin E (E). This new and potentially valuable animal model proved to be very sensitive to the toxicity of this nitro drug. The 48-hour LD₅₀ for nitrofurantoin decreased from 148 mg/kg in the Se- and E-supplemented chicks to 53 mg/kg in the Se- and E-deficient chicks. The addition of Se (0.10 ppm as Na₂SeO₃) alone, but not E (100 IU/kg diet as dl--tocopheryl acetate) reduced the toxicity of nitrofurantoin, so that the LD₅₀ for the chicks given Se alone was the same as the LD₅₀ for the E- and Se-fed chicks. Se and E deficiency significantly decreased the Se-dependent glutathione peroxidase and the plasma tocopherol levels. Hepatic glutathione content, hepatic catalase and superoxide dismutase were unchanged by the dietary treatments. However, a toxic dose of nitrofurantoin significantly decreased hepatic glutathione content over time. These data support the concept that the toxicity of this drug may be mediated in part by an oxidative stress generated by the futile reductive metabolism of the parent compound.

KEY WORDS: • nitrofurantoin • selenium • vitamin E • toxicity

¹ A preliminary report has appeared elsewhere in the Proceedings of the Fourth International Symposium on Microsomes and Drug Oxidations held at Ann Arbor, Michigan, July 16, 1979. Peterson, F. J., Combs, G. F., Jr., Holtzman, J. L. and Mason, R. P. (1980) Effect of selenium and vitamin E deBciency on the toxicity of nitrofurantoin in the chick. In: Microsomes, Drug Oxidations and Chemical Carcinogenesis (Coon, M. J., Conney, A. H., Estabrook, R. W., Gelboin, H. V., Gillette, J. R. & O'Brien, P. J., eds.), vol. II, pp. 873–876, Academic Press, New York.

² Send reprint requests to: Dr. Francis J. Peterson, Department of Poultry and Avian Sciences, Division of Nutritional Sciences, Rice Hall, Cornell University, Ithaca, NY 14853.

³ Present address: Laboratory of Environmental Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.

Manuscript received 11 December 1981.