Evaluation of lipid-based carrier systems and inclusion complexes of diethyldithiocarbamate-iron to trap nitric oxide in biological systems.
The success of spin trapping techniques in vivo hinges on whether spin traps with high trapping efficiency and biocompatibility can be developed. Currently, two iron chelates based on the dithiocarbamate structure (hydrophilic ferro-di(N-methyl-D-glucamine-dithiocarbamate, or Fe(II)-MGD, and lipophilic ferro-di(diethyldithiocarbamate), or Fe(II)-DETC), are used for spin trapping of nitric oxide (NO) in biologic systems. However, detection efficiency is hampered by a complex redox chemistry for Fe(II)-MGD and by the insolubility of Fe(II)-DETC in water. To circumvent these problems, two new spin trap formulations based on Fe(II)-DETC were developed: a lipid-based carrier system stabilized by lecithin and inclusion complexes in hydroxypropyl-beta-cyclodextrin. The capability of these two systems to trap NO was determined and compared to the standard spin traps in vitro (in the presence of an NO donor) and in vivo (after induction of septic shock in mice). The sensitivity of the detection of NO was significantly increased (by a factor of 4) using the lipid-based carrier systems or inclusion complexes compared to the standard spin trap agents.
Charlier
Nicolas
N
Laboratory of Medicinal Chemistry and Radiopharmacy, Biomedical Resonance Unit, Université Catholique de Louvain, Brussels, Belgium.
Préat
Véronique
V
Gallez
Bernard
B
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry; D004050:Ditiocarb / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D008297:Male; D051379:Mice; D008956:Models, Chemical; D009569:Nitric Oxide / Q000032:analysis / Q000737:chemistry*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry; D012772:Shock, Septic / Q000378:metabolism*; D019097:Spin Trapping
D002614:Chelating Agents; D003505:Cyclodextrins; D010713:Phosphatidylcholines; D009569:Nitric Oxide; D004050:Ditiocarb