Antioxidant capacity of mononitrosyl-iron-dithiocarbamate complexes: Implications for NO trapping

Using EPR spectroscopy, we show that the water-soluble mononitrosyl iron co mplexes with N-methyl-D-glucamine dithiocarbamate (MNIC-MGD) ligands can ea sily react with superoxide and with peroxynitrite. The reaction with supero xide transforms the paramagnetic MNIC-MGD complex into an EPR silent comple x with a reaction rate of 3 x 10(7) (M.s)(-1). Suppletion of ascorbate part ially restores the complexes to their original paramagnetic state. We propo se that the reaction of MNIC-MGD with either superoxide or peroxynitrite le ads to identical EPR silent complexes. Our results have important implicati ons for the technique of NO trapping in biosystems with Fe-dithiocarbamate complexes, where mononitrosyl-iron complexes (hydrophilic as well as hydrop hobic) are formed as adducts in the trapping reaction. This principle is il lustrated by NO trapping experiments on viable cultured endothelial cells. We find that MNIC-MGD acts as a very potent and water-soluble antioxidant w ith an efficiency exceeding most SOD mimics. Moreover, by accounting for th e EPR silent fraction of iron complexes, the sensitivity of NO trapping can be enhanced considerably. The method was demonstrated for hydrophobic iron -dithiocarbamate complexes in endothelial cell cultures, where sensitivity for NO detection was enhanced by a factor of 5. (C) 2001 Elsevier Science I nc.