Dataset Information

Effects of a Compound from the Group of Substituted Thiadiazines with Hypothermia Inducing Properties on Brain Metabolism in Rats, a Study In Vivo and In Vitro

ABSTRACT: 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 thermoregulation 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 1.5 °C. 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.

INSTRUMENT(S): Bruker

SUBMITTER: Oleg Shevelev

PROVIDER: MTBLS482 | MetaboLights | 2018-07-27

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS482	Other
	FILES	Other
	a_MTBLS482_metabolite_profiling_NMR_spectroscopy.txt	Txt
	a_l17_metabolite_profiling_NMR_spectroscopy-1.txt	Txt
	a_l17_metabolite_profiling_NMR_spectroscopy.txt	Txt

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Publications

Effects of a compound from the group of substituted thiadiazines with hypothermia inducing properties on brain metabolism in rats, a study in vivo and in vitro.

Shevelev O B OB Illarionova N B NB Petrovski D V DV Sarapultsev A P AP Chupakhin O N ON Moshkin M P MP

PloS one 20170705 7

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 thermoregulation as well as act via inhibition of energy metabolism. We tested the hypothesis that L-17 may induce hypothermia by directly inhibiting energy metabolism. ...[more]

PMID: 28678857

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