Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Kupats 2020 Oxid Med Cell Longev

From Bioblast
Revision as of 17:16, 26 November 2020 by Plangger Mario (talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
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