A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia–reperfusion injury in mice; Neuroscience Letters; Vol. 618

Dades bibliogràfiques
Parent link:	Neuroscience Letters.— , 1975- Vol. 618.— 2016.— [P. 45–49]
Autor corporatiu:	Национальный исследовательский Томский политехнический университет Управление проректора по научной работе и инновациям Центр RASA в Томске Лаборатория изучения механизмов нейропротекции, Национальный исследовательский Томский политехнический университет Институт физики высоких технологий Кафедра биотехнологии и органической химии
Altres autors:	Atochin D. N. Dmitry Nikolaevich, Schepetkin (Shchepyotkin) I. A. Igor Aleksandrovich, Khlebnikov A. I. Andrey Ivanovich, Seledtsov V. I. Victor I., Swanson H. Helen, Quinn M. T. Mark T., Huang P. L. Paul L.
Sumari:	Title screen The c-Jun N-terminal kinase (JNK) has been shown to be an important regulator of neuronal cell death. Previously, we synthesized the sodium salt of 11H-indeno[1,2-b]quinoxalin-11-one (IQ-1S) and demonstrated that it was a high-affinity inhibitor of the JNK family. In the present work, we found that IQ-1S could release nitric oxide (NO) during its enzymatic metabolism by liver microsomes. Moreover, serum nitrite/nitrate concentration in mice increased after intraperitoneal injection of IQ-1S. Because of these dual actions as JNK inhibitor and NO-donor, the therapeutic potential of IQ-1S was evaluated in an animal stroke model. We subjected wild-type C57BL6 mice to focal ischemia (30 min) with subsequent reperfusion (48 h). Mice were treated with IQ-1S (25 mg/kg) suspended in 10% solutol or with vehicle alone 30 min before and 24 h after middle cerebral artery (MCA) occlusion (MCAO). Using laser-Doppler flowmetry, we monitored cerebral blood flow (CBF) above the MCA during 30 min of MCAO provoked by a filament and during the first 30 min of subsequent reperfusion. In mice treated with IQ-1S, ischemic and reperfusion values of CBF were not different from vehicle-treated mice. However, IQ-1S treated mice demonstrated markedly reduced neurological deficit and infarct volumes as compared with vehicle-treated mice after 48 h of reperfusion. Our results indicate that the novel JNK inhibitor releases NO during its oxidoreductive bioconversion and improves stroke outcome in a mouse model of cerebral reperfusion. We conclude that IQ-1S is a promising dual functional agent for the treatment of cerebral ischemia and reperfusion injury. Режим доступа: по договору с организацией-держателем ресурса
Idioma:	anglès
Publicat:	2016
Matèries:	электронный ресурс труды учёных ТПУ
Accés en línia:	http://dx.doi.org/10.1016/j.neulet.2016.02.033
Format:	Electrònic Capítol de llibre
KOHA link:	https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=648023