Тип публикации: статья из журнала

Год издания: 2017

Идентификатор DOI: 10.1371/journal.pone.0180739

Ключевые слова: Thiadiazines

Аннотация: The aim of the present study was to examine how administration of a compound of 1,3,4-thiadiazine class 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17) with hypothermia inducing properties affects the brain metabolism. The mechanism by which L-17 induces hypothermia is unknown; it may involve hypothalamic central thПоказать полностьюermoregulation as well as act via inhibition of energy metabolism. We tested the hypothesis that L-17 may induce hypothermia by directly inhibiting energy metabolism. The study in vivo was carried out on Sprague-Dawley adult rats. Two doses of L-17 were administered (190 mg/ kg and 760 mg/kg). Brain metabolites were analyzed in control and treated groups using magnetic resonance spectroscopy, along with blood flow rate measurements in carotid arteries and body temperature measurements. Further in vitro studies on primary cultures from rat hippocampus were carried out to perform a mitochondria function test of L-17 pre-incubation (100 μM, 30 min). Analysis of brain metabolites showed no significant changes in 190 mg/kg treated group along with a significant reduction in body temperature by 1.5C. However, administration of L-17 in higher dose 760 mg/kg provoked changes in brain metabolites indicative of neurotoxicity as well as reduction in carotid arteries flow rate. In addition, a balance change of excitatory and inhibitory neurotransmitters was observed. The L-17 pre-incubation with cell primary cultures from rat brain showed no significant changes in mitochondrial function. The results obtained in the study indicate that acute administration of L-17 190 mg/kg in rats induces mild hypothermia with no adverse effects onto brain metabolism. © 2017 Shevelev et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Журнал: PLoS ONE

Выпуск журнала: Vol. 12, Is. 7

Номера страниц: 0180739

ISSN журнала: 19326203

Издатель: Public Library of Science

• Shevelev O.B. (Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation)
• Illarionova N.B. (Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation)
• Petrovski D.V. (Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation)
• Sarapultsev A.P. (Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Ekaterinburg, Russian Federation, Federal State Autonomous Educational Institution of Higher Professional Education, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Ekaterinburg, Russian Federation)
• Chupakhin O.N. (Federal State Autonomous Educational Institution of Higher Professional Education, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Ekaterinburg, Russian Federation, Institute of Organic Synthesis, Ural Division of Russian Academy of Sciences, Ekaterinburg, Russian Federation)
• Moshkin M.P. (Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation, Tomsk State University, Department of Vertebrate Zoology, Tomsk, Russian Federation)

• Scopus