Page 55
Journal of Organic & Inorganic Chemistry
ISSN 2472-1123
2
n d
E d i t i o n o f E u r o S c i C o n C o n f e r e n c e o n
Chemistry
F e b r u a r y 1 9 - 2 0 , 2 0 1 9
P r a g u e , C z e c h R e p u b l i c
Chemistry 2019
N
itric oxide (NO) has been implicated recently in a number of diverse physiological processes, including smooth muscle
relaxation, inhibition of platelet adhesion and neurotransmission. Besides these beneficial functions, NO exhibits cytotoxic
affect such as inactivating biologically important mitochondrial respiratory enzymes and neutrophil NADPH oxidase. To
understand the mechanism by which NO is synthesized by nitric oxide synthase (NOS) in tissues and how NO mediates various
physiological responses, it is useful to be able to observe real time NO generation at the site of production. We have shown
direct, real-time, in-vivo measurement of nitric oxide (NO) in mice using the water soluble metal chelator complex, N-methyl-D-
glucamine dithiocarbamate (MGD), and Fe(II) and the lipophilic reagent, N, N-diethyl-dithiocarbamate (DETC), as monitored by
electron paramagnetic resonance (EPR) at L-band. The EPR spectrum from the product [(MGD)2-Fe (II)-NO] or [(DETC)-Fe(II)-
NO] was observed noninvasively in lipopolysaccharide (LPS)-treated mice. In-vivo EPR measurements of [(MGD)2-Fe(II)-NO] at
several regions in the body (from the head to the tail) indicated that the NO was generated mostly in the upper abdomen near
the liver. This was confirmed by ex-vivo EPR measurements on isolated organs where the higher NO levels were detected in the
liver and kidney. In the case of [(DETC)-Fe(II)-NO], we were successful in observing relatively high concentrations of NO trapped
in excised brain tissue. The spectroscopic results also showed that both the DETC and Fe(II) independently cross the blood brain
barrier and combine with NO in the lipid regions of certain parts of the brain. Lastly, the NO-adduct detected in LPS-treated mice
brains was not inducible NOS, but probably rather constitutive NOS, since it was not suppressed by the administration, prior to
LPS injection, of phenyl N-tert-butyl nitrone (PBN), an inhibitor of the expression of induced nitric oxide synthase (iNOS).
berliner@du.eduNovel methods of detecting oxygen and nitrogen
reactive species
Lawrence J Berliner
University of Denver, USA
J Org Inorg Chem 2019, Volume: 5
DOI: 10.21767/2472-1123-C1-021