RESUMEN
3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone) is a synthetic one-electron antioxidant used as a drug for treatment against acute phase cerebral infarction in Japan. This drug also reacts with two-electron oxidants like peroxynitrite to give predominantly 4-nitrosoedaravone but no one-electron oxidation products. It is believed that this plays a significant role in amelioration of amyotrophic lateral sclerosis. The drug was approved for treatment of amyotrophic lateral sclerosis in Japan and USA in 2015 and 2017, respectively. In this study, we examined the reaction of edaravone with another two-electron oxidant, hypochlorite anion (ClO-). Edaravone reacted with ClO- in 50% methanolic phosphate buffer (pH 7.4) solution containing typical two-electron reductants, such as glutathione, cysteine, methionine, and uric acid, as internal references. The concentration of edaravone decreased at a similar rate as each co-existing reference, indicating that it showed comparable reactivity toward ClO- as those references. Furthermore, 4-Cl-edaravone and (E)-2-chloro-3-[(E)-phenyldiazenyl]-2-butenoic acid (CPB) were identified as primary and end products, respectively, and no one-electron oxidation products were detected. These results suggest that edaravone treatment can bring greater benefit against ClO--related injury such as inflammation, and 4-Cl-edaravone and CPB can be good biomarkers for ClO--induced oxidative stress.
RESUMEN
We have developed a versatile, high-yield synthesis of diarylchloroniums/λ3-chloranes through the reaction of various chloroarenes with readily prepared mesityldiazonium tetrakis(pentafluorophenyl)borate under mild conditions. The scope of the reaction is broad, including ArCl, ArBr, and ArI. The diarylchloroniums/λ3-chloranes prepared here show unique reactivity in various respects, enabling intermolecular electrophilic arylation reaction of weak nucleophiles, and chlorane-halogane exchange reaction.
RESUMEN
In vitro block preparations of the central nervous system (CNS) are particularly valuable for study of central neuronal mechanisms controlling the respiratory and locomotor rhythms. No comparable in vitro preparation has been described previously, however, for analysis of analogous feeding rhythms. In this chapter, we present such a model. It is comprised of an in vitro brainstem-spinal cord preparation isolated from the newborn rat and mouse. Bath application to this preparation of N-methyl-D-aspartate (NMDA) induces rhythmical burst activity in the V, VII and XII nerves, which, collectively, is indicative of feeding behavior. Selected transections of the brainstem reveal that the central sucking rhythm generators for such V, VII and XII activity are separate from one another, and located segmentally in the brainstem at the level of their respective motor nuclei. We believe that use of this in vitro preparation will advance understanding of the central neuronal mechanisms controlling sucking and mastication, and the developmental transition from sucking to mastication.