Abstract
IN 1957, Haley et al. 1 found that quinoxaline-1,4-di-N-oxide reduced X-radiation mortality in mice by 50 per cent. Two mechanisms were involved, reduction of bacteræmia1 and interaction with X-ray-produced oxidizing radicals2. Comparisons have been made of other N-oxides (Table 1) using groups of 20 CF-1 mice and the same radiation conditions as before1. The 250 mgm./kgm. oral dose of drugs was given 24 hr. prior to irradiation with 550 r. The two quinoxaline derivatives significantly increased the ST 50 day but had less effect on total survival than quinoxaline-1,4-di-N-oxide. Erythromycin N-oxide significantly reduced the ST 50 day and total survival while its anhydro derivative was equivalent to quinoxaline-1,4-di-N-oxide as a radiation prophylactic. All the above compounds are readily absorbed, excreted slowly in the urine and exert antibiotic effects so the radiation bacteræmia could be reduced. On the other hand not all of them can interact with equal facility with the radiation-produced oxidizing radicals. Examination of the chemical structures involved indicated that an amine oxide either in an unsaturated ring, for example, quinoxaline or within one carbon atom of a double bond, for example, anhydroerythromycin is necessary if oxidizing radicals are to be prevented from exerting their deleterious effects. In the dimethyl-substituted quinoxaline compounds difficulties in oxidizing the methyl groups are probably the reason for the decrease in protectant activity even though Francis et al. 4 showed that hydroxylation in the 2 position occurs in vivo. With erythromycin N-oxide, the double bond is lacking and the compound can be oxidized only with difficulty even in vitro 5. Thus, it would appear that amine oxides with the above chemical structures can reduce mortality from ionizing radiation when administered orally 24 hr. prior to exposure.
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Haley, T. J., Flesher, A. M., Veomett, R., and Vincent, J., Proc. Soc. Exp. Biol. Med., N.Y., 96, 579 (1957).
Haley, T. J., Abstr. of Papers, Amer. Chem. Soc., 134th Meeting, Sept. 7–12, 1958, 19-0.
Litchfield, jun., J. T., J. Pharmacol., 97, 399 (1949).
Francis, J., Landquist, J. K., Levi, A. A., Silk, J. A., and Thorp, J. M., Biochem. J., 63, 455 (1956).
Flynn, E. H., Sigal, jun., M. V., Wiley, P. F., and Gerzon, K., J. Amer. Chem. Soc., 76, 3121 (1954).
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HALEY, T., FLESHER, A. & KOMESU, N. Prophylactic Effects of Amine Oxides in Radiation Injury in Mice. Nature 184, 198 (1959). https://doi.org/10.1038/184198a0
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DOI: https://doi.org/10.1038/184198a0
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