Biological spin trapping II. Toxicity of nitrone spin traps: dose-ranging in the rat

To obtain the strongest possible free radical spin adduct signal using the electron paramagnetic resonance spectroscopy-spin trapping technique, it is desirable to load an animal with the highest dose of spin trap possible. One hundred and twenty six male Sprague-Dawley rats were used to establish t...

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Bibliographic Details
Published in:Journal of biochemical and biophysical methods 1995-11, Vol.30 (4), p.239-247
Main Authors: Janzen, Edward G., Poyer, J.Lee, Schaefer, Carl F., Downs, Paula E., DuBose, Coit M.
Format: Article
Language:English
Subjects:
Animals
Cyclic N-Oxides - toxicity
Dose-Response Relationship, Drug
Male
Nitrogen Oxides - toxicity
Rats
Rats, Sprague-Dawley
Spin Labels
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Summary:To obtain the strongest possible free radical spin adduct signal using the electron paramagnetic resonance spectroscopy-spin trapping technique, it is desirable to load an animal with the highest dose of spin trap possible. One hundred and twenty six male Sprague-Dawley rats were used to establish the toxic dose range for PBN (α-phenyl N- tert butyl nitrone) and 18 other similar spin traps. The lethal dose of PBN was found to be approximately 100 mg/100 g BW (0.564 mmol/100 g). The 18 other compounds were then tested, and their toxicities were gauged in terms of molar equivalents to PBN. Of these spin traps, DMPO (5,5-dimethyl-1-pyrroline-N-oxide) was found to be the least toxic (no toxic signs at twice the lethal dose for PBN) while 2,6-difluoro-PBN and M 4PO (3,3,5,5-tetramethyl-1-pyrroline-N-oxide) were the most toxic, both causing death at one eighth the PBN-equivalent lethal dose. Nine of the 18 nitrones appeared non-toxic at the 0.25 PBN-equivalent lethal dose level.
ISSN:0165-022X
1872-857X
DOI:10.1016/0165-022X(95)00012-1