Real-time monitoring of drug-induced changes in the stomach acidity of living rats using improved pH-sensitive nitroxides and low-field EPR techniques

Real-time monitoring of drug-induced changes in the stomach acidity of living rats using improved pH-sensitive nitroxides and low-field EPR techniques Научная публикация

Журнал

Journal of Magnetic Resonance
ISSN: 1090-7807

Вых. Данные

Год: 2006, Том: 182, Номер: 1, Страницы: 1-11 Страниц : DOI: 10.1016/j.jmr.2006.06.002

Ключевые слова

nitroxide; in vivo EPR techniques; in vivo pH measurement; stomach acidity

Авторы

Potapenko Dmitrii I. , Foster Margaret A. , Lurie David J. , Kirilyuk Igor A. , Hutchison James M. S. , Grigor'ev Igor A. , Bagryanskaya Elena G. , Khramtsov Valery V.

Организации

1	(Данные Web of science) Russian Acad Sci, Inst Chem Kinet & Combust, Novosibirsk 630090, Russia
2	(Данные Web of science) NN Vorozhtsov Novosibirsk Inst Organ Chem, Novosibirsk, Russia
3	(Данные Web of science) Univ Aberdeen, Sch Med Sci, Aberdeen AB25 2ZD, Scotland
4	(Данные Web of science) Int Tomog Ctr, Novosibirsk, Russia
5	(Данные Web of science) Ohio State Univ, Dorothy

New improved pH-sensitive nitroxides were applied for in vivo studies. An increased stability of the probes towards reduction was achieved by the introduction of the bulky ethyl groups in the vicinity of the paramagnetic N-O fragment. In addition, the range of pH sensitivity of the approach was extended by the synthesis of probes with two ionizable groups, and, therefore, with two pK(a) values. Stability towards reduction and spectral characteristics of the three new probes were determined in vitro using 290 MHz radiofrequency (RF)- and X-band electron paramagnetic resonance (EPR), longitudinally detected EPR (LODEPR), and field-cycled dynamic nuclear polarization (FC-DNP) techniques. The newly synthesized probe, 4-[bis(2-hydroxyethyl)amino]-2-pyridine-4-yl-2,5,5-triethyl-2,5-,dihydro-1H-imidazol-oxyl, was found to be the most appropriate for the application in the stomach due to both higher stability and convenient pH sensitivity range from pH 1.8 to 6. LODEPR, FC-DNP and proton-electron double resonance imaging (PEDRI) techniques were used to detect the nitroxide localization and acidity in the rat stomach. Improved probe characteristics allowed us to follow in vivo the drug-induced perturbation in the stomach acidity and its normalization afterwards during I h or longer period of time. The results show the applicability of the techniques for monitoring drug pharmacology and disease in the living animals. (c) 2006 Elsevier Inc. All rights reserved.

Potapenko D.I. , Foster M.A. , Lurie D.J. , Kirilyuk I.A. , Hutchison J.M.S. , Grigor'ev I.A. , Bagryanskaya E.G. , Khramtsov V.V.
Real-time monitoring of drug-induced changes in the stomach acidity of living rats using improved pH-sensitive nitroxides and low-field EPR techniques
Journal of Magnetic Resonance. 2006. V.182. N1. P.1-11. DOI: 10.1016/j.jmr.2006.06.002 WOS Scopus РИНЦ

Опубликована в печати:

1 сент. 2006 г.

Web of science	WOS:000240609500001
Scopus	2-s2.0-33747871573
РИНЦ	13525513
OpenAlex	W1973351633