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Kupats 2020 Oxid Med Cell Longev

From Bioblast
Publications in the MiPMap
Kupats E, Stelfa G, Zvejniece B, Grinberga S, Vavers E, Makrecka-Kuka M, Svalbe B, Zvejniece L, Dambrova M (2020) Mitochondrial-protective effects of R-phenibut after experimental traumatic brain injury. Oxid Med Cell Longev 2020:9364598.

» Open Access

Kupats Einars, Stelfa Gundega, Zvejniece Baiba, Grinberga Solveiga, Vavers Edijs, Makrecka-Kuka Marina, Svalbe Baiba, Zvejniece Liga, Dambrova Maija (2020) Oxid Med Cell Longev

Abstract: Altered neuronal Ca2+ homeostasis and mitochondrial dysfunction play a central role in the pathogenesis of traumatic brain injury (TBI). R-Phenibut ((3R)-phenyl-4-aminobutyric acid) is an antagonist of the α2δ subunit of voltage-dependent calcium channels (VDCC) and an agonist of gamma-aminobutyric acid B (GABA-B) receptors. The aim of this study was to evaluate the potential therapeutic effects of R-phenibut following the lateral fluid percussion injury (latFPI) model of TBI in mice and the impact of R- and S-phenibut on mitochondrial functionality in vitro. By determining the bioavailability of R-phenibut in the mouse brain tissue and plasma, we found that R-phenibut (50 mg/kg) reached the brain tissue 15 min after intraperitoneal (i.p.) and peroral (p.o.) injections. The maximal concentration of R-phenibut in the brain tissues was 0.6 μg/g and 0.2 μg/g tissue after i.p. and p.o. administration, respectively. Male Swiss-Webster mice received i.p. injections of R-phenibut at doses of 10 or 50 mg/kg 2 h after TBI and then once daily for 7 days. R-Phenibut treatment at the dose of 50 mg/kg significantly ameliorated functional deficits after TBI on postinjury days 1, 4, and 7. Seven days after TBI, the number of Nissl-stained dark neurons (N-DNs) and interleukin-1beta (IL-1β) expression in the cerebral neocortex in the area of cortical impact were reduced. Moreover, the addition of R- and S-phenibut at a concentration of 0.5 μg/ml inhibited calcium-induced mitochondrial swelling in the brain homogenate and prevented anoxia-reoxygenation-induced increases in mitochondrial H2O2 production and the H2O2/O ratio. Taken together, these results suggest that R-phenibut could serve as a neuroprotective agent and promising drug candidate for treating TBI.

Bioblast editor: Plangger M O2k-Network Lab: LV Riga Makrecka-Kuka M

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Other 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Homogenate, Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k, O2k-Fluorometer 

2020-11, AmR