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 the toxic dose range for PBN (alpha-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 M4PO (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.
Janzen
E G
EG
National Biomedical Center for Spin Trapping and Free Radicals, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Poyer
J L
JL
Schaefer
C F
CF
Downs
P E
PE
DuBose
C M
CM
D000818:Animals; D003497:Cyclic N-Oxides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009589:Nitrogen Oxides / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels
D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D013113:Spin Labels; C051831:3,3,5,5-tetramethyl-1-pyrroline N-oxide; C029217:phenyl-N-tert-butylnitrone; C017245:5,5-dimethyl-1-pyrroline-1-oxide