The excretion mechanism of the spin label proxyl carboxylic acid (PCA) from the rat monitored by X-band ESR and PEDRI.
Proton electron double resonance imaging (PEDRI) was used for monitoring in vivo the distribution, metabolism and, in particular, the excretion mechanism of the exogenous nitroxide free radical proxyl carboxylic acid (PCA) in the rat. PCA clearance half-lives through liver, abdominal vessels, and renal tissues were determined from a series of PEDRI images for normal rats (n = 5) and rats treated with probenecid (n = 5), a competitive inhibitor of the tubular secretion process. The approximately doubled renal half-lives of the treated animals suggest that tubular secretion accounts for about 50% of PCA renal loss in the normal rat and reabsorption is insignificant. PCA binding to bovine serum albumin was investigated by X-band ESR and the bound fraction was found to be less than 10% of the total PCA. Most probably, PCA binds to hydrophilic sites. Blood PCA concentration investigated by X-band ESR exhibited biphasic behavior and PEDRI results confirmed the in vivo metabolic reduction of PCA by rat liver cells.
Seimenis
I
I
Department of Biomedical Physics and Bioengineering, University of Aberdeen, Foresterhill, UK.
Foster
M A
MA
Lurie
D J
DJ
Hutchison
J M
JM
Whiting
P H
PH
Payne
S
S
D000818:Animals; D001665:Binding Sites; D003497:Cyclic N-Oxides / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D006207:Half-Life; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods; D011838:Radiation-Sensitizing Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels
D003497:Cyclic N-Oxides; D011838:Radiation-Sensitizing Agents; D013113:Spin Labels; C032289:2,2,5,5-tetramethyl-1-pyrrolidinyloxy-3-carboxylic acid