Evaluation of DEPMPO as a spin trapping agent in biological systems.
Cellular toxicity, pharmacokinetics, and the in vitro and in vivo stability of the SO3*- spin adduct of the spin trap, 5-diethoxyphosphoryl-5-methyl-1-pyrroline-n-oxide (DEPMPO), was investigated, and the results were compared with those of the widely used spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Similar to DMPO, DEPMPO was quickly taken up (<15 min) after intraperitoneal injection, and distributed evenly in the liver, heart, and blood of the mice. In the presence of ascorbate the in vitro stability of the adduct DEPMPO/SO3*- was 7 times better than DMPO/SO3*-. Under in vivo conditions, the spin adduct DEPMPO/SO3*- was 2-4 times more stable than DMPO/ SO3*-, depending on the route of administration of the adducts. Using a low frequency EPR spectrometer, we were able to observe the spin trapped SO3*- radical both with DMPO and DEPMPO directly in the intact mouse. DEPMPO had a detectable spin adduct signal at a concentration as low as 1 mM, as compared to 5 mM for DMPO. We conclude that DEPMPO is potentially a good candidate for trapping radicals in functioning biological systems, and represents an improvement over the commonly used trap DMPO.
Liu
K J
KJ
Department of Radiology, Dartmouth Medical School, Hanover, NH 03755, USA. jim.liu@dartmouth.edu
Miyake
M
M
Panz
T
T
Swartz
H
H
D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005609:Free Radicals; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D013113:Spin Labels; D013447:Sulfites / Q000737:chemistry; D014018:Tissue Distribution
D003497:Cyclic N-Oxides; D005609:Free Radicals; D013113:Spin Labels; D013447:Sulfites; C098505:5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide; C017245:5,5-dimethyl-1-pyrroline-1-oxide