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100			_a20160505a2016 k y0engy50 ba
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200	1		_aA novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia–reperfusion injury in mice _fD. N. Atochin, I. A. Schepetkin (Shchepyotkin), A. I. Khlebnikov [et al.]
203			_aText _celectronic
300			_aTitle screen
320			_a[References.: p. 49 (45 tit.)]
330			_aThe 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.
333			_aРежим доступа: по договору с организацией-держателем ресурса
461			_tNeuroscience Letters _d1975-
463			_tVol. 618 _v[P. 45–49] _d2016
610	1		_aэлектронный ресурс
610	1		_aтруды учёных ТПУ
701		1	_aAtochin _bD. N. _cneuroscientist _cThe Head of the Laboratory of Tomsk Polytechnic University _f1960- _gDmitry Nikolaevich _2stltpush _3(RuTPU)RU\TPU\pers\37514
701		1	_aSchepetkin (Shchepyotkin) _bI. A. _cdoctor-biophysicist _cleading researcher of Tomsk Polytechnic University, candidate of medical science _f1962- _gIgor Aleksandrovich _2stltpush _3(RuTPU)RU\TPU\pers\37358
701		1	_aKhlebnikov _bA. I. _cChemist _cProfessor of Tomsk Polytechnic University _f1963- _gAndrey Ivanovich _2stltpush _3(RuTPU)RU\TPU\pers\33927
701		1	_aSeledtsov _bV. I. _gVictor I.
701		1	_aSwanson _bH. _gHelen
701		1	_aQuinn _bM. T. _gMark T.
701		1	_aHuang _bP. L. _gPaul L.
712	0	2	_aНациональный исследовательский Томский политехнический университет (ТПУ) _bУправление проректора по научной работе и инновациям (НРиИ) _bЛаборатория изучения механизмов нейропротекции
712	0	2	_aНациональный исследовательский Томский политехнический университет (ТПУ) _bИнститут физики высоких технологий (ИФВТ) _bКафедра биотехнологии и органической химии (БИОХ) _h6810 _2stltpush _3(RuTPU)RU\TPU\col\18693
801		2	_aRU _b63413507 _c20201103 _gRCR
856	4		_uhttp://dx.doi.org/10.1016/j.neulet.2016.02.033
942			_cCF