Difference between revisions of "Kupats 2020 Oxid Med Cell Longev"
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|journal=Oxid Med Cell Longev | |journal=Oxid Med Cell Longev | ||
|abstract=Altered neuronal | |abstract=Altered neuronal Ca<sup>2+</sup> 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 H<sub>2</sub>O<sub>2</sub>/O ratio. Taken together, these results suggest that R-phenibut could serve as a neuroprotective agent and promising drug candidate for treating TBI. | ||
|editor=[[Plangger M]] | |editor=[[Plangger M]] | ||
|mipnetlab=LV Riga Makrecka-Kuka M | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, Pharmacology;toxicology | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=2020-11 | |additional=2020-11 | ||
}} | }} |
Revision as of 17:12, 26 November 2020
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 . |
Kupats E, Stelfa G, Zvejniece B, Grinberga S, Vavers E, Makrecka-Kuka M, Svalbe B, Zvejniece L, Dambrova M (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
HRR: Oxygraph-2k
2020-11