Modulatory effects of vitamin B3 and its derivative on the levels of apoptotic and vascular regulators and cytoskeletal proteins in diabetic rat brain as signs of neuroprotection

Tykhonenko, T.; Guzyk, M. M.; Tykhomyrov, А. A.; Korsa, V V; Yanitska, Lesya; Kuchmerovska, Т. М.

doi:10.1016/j.bbagen.2022.130207

Cited by 8 publications

(5 citation statements)

References 57 publications

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“…Such an effect is generally characteristic of benzodiazepines, which, for example, in Alzheimer's disease improve clinical outcomes due to allosteric modulation of the GABA effect [29]. The results of our study are in agreement with very recent report, in which N-GABA treatment of rats with streptozotocin-induced diabetes has been shown to improve angiogenic signaling, inhibit apoptosis, and preserve the integrity of blood-brain barrier in brain tissue [30]. Thus, restoration of GABA-ergic signaling can be used as a promising therapeutic option for the correction of neuronal dysfunction in DR.…”

Section: Fig 3 Quantification Of Vascular Endothelial Growth Factor (...supporting

confidence: 92%

Benzodiazepine receptor agonist carbacetam modulates the level of vascular endothelial growth factor in the retina of rats with streptozotocin-induced diabetes

Ziablitsev,

Zhupan,

Tykhomyrov

et al. 2023

Ukr.Biochem.J.

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One of the primary mechanisms of retinal neurodegeneration in diabetes mellitus is gamma-aminobutyric acid (GABA) deficiency that makes the use of GABA-benzodiazepine receptor modulators a promising option for the correction of this diabetic complication. The aim of this study was to determine the effect of the benzodiazepine receptor agonist carbacetam on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in retina of rats with hyperglycemia. Experimental diabetes was modeled by a single administration of streptozotocin (50 mg/kg) to three-month-old male Wistar rats. Immunoblotting and immunohistochemical studies were performed using monoclonal antibodies against VEGF and HIF-1α. It was shown that the development of diabetic retinopathy (DR) at the early stages was accompanied by a progressive multifold increase in the retina content of VEGF on 7-28 days and HIF-1α on 28th day. Insulin and insulin+carbacetam treatment significantly alleviated diabetes-induced overexpression of both HIF-1α and VEGF. Carbacetam was shown to block the diabetogenic increase in VEGF content in retina. The introduction of insulin with carbacetam significantly reduced the expression of VEGF and the development of specific morphological manifestations of DR. Thus, restoration of GABA-ergic signaling can be used as a promising therapeutic option for the correction of DR disorders. Keywords: carbacetam, GABA-benzodiazepine receptors, HIF-1α hyperglycemia, retinopathy, streptozotocin-induced diabetes, VEGF

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Section: Fig 3 Quantification Of Vascular Endothelial Growth Factor (...supporting

confidence: 92%

Benzodiazepine receptor agonist carbacetam modulates the level of vascular endothelial growth factor in the retina of rats with streptozotocin-induced diabetes

Ziablitsev,

Zhupan,

Tykhomyrov

et al. 2023

Ukr.Biochem.J.

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“…Недавнее исследование T. Tykhonenko et al уточнило механизмы нейропротективной активности никотинамида и его производных, отметив их способность подавлять нейровоспаление и апоптоз [59]. В экспериментальной модели крыс с сахарным диабетом как для никотинамида, так и для никотиноил гамма-аминомасляной кислоты было показано уменьшение уровней NF-κB, активация которого, как было указано ранее, повышает экспрессию генов -регуляторов продукции провоспалительных цитокинов, хемокинов, увеличивает продукцию оксида азота (II), перекиси водорода, простагландина E2 [60] (рис.…”

Section: применение ноотропов и нейропротекторов для коррекции додеме...unclassified

“…В экспериментальной модели крыс с сахарным диабетом как для никотинамида, так и для никотиноил гамма-аминомасляной кислоты было показано уменьшение уровней NF-κB, активация которого, как было указано ранее, повышает экспрессию генов -регуляторов продукции провоспалительных цитокинов, хемокинов, увеличивает продукцию оксида азота (II), перекиси водорода, простагландина E2 [60] (рис. 3) и белка BAX (BAX protein)одного из индукторов апоптоза -в мозге крыс [59]. Кроме того, в исследованиях других ГАМК-эргических препаратов показано, что активация ГАМК В -рецептора может ингибировать выработку провоспалительного IL-1β путем подавления активации сигнального пути NF-κB [61].…”

Section: применение ноотропов и нейропротекторов для коррекции додеме...unclassified

“…Тестируемые T. Tykhonenko et al соединения улучшили нарушенную гипергликемией экспрессию ангиогенных и цитоскелетных белков, в частности, VEGF (vascular endothelial growth factor -сосудистый эндотелиальный фактор роста) и nNOS (neuronal nitric oxide synthaseнейрональная синтаза оксида азота) [59]. Следует отметить, что оксид азота (II), полученный посредством стимуляции nNOS, является нейротрансмиттером и способен регулировать церебральный кровоток, участвует в синаптической интеграции взрослых нейронов и формировании памяти, передаче болевых сигналов [62].…”

Section: применение ноотропов и нейропротекторов для коррекции додеме...unclassified

“…Кроме этого, никотинамид и никотиноил гаммааминомасляная кислота нормализуют проницаемость ГЭБ, что показано путем измерения содержания GFAP (glial fibrillary acidic protein -глиальный фибриллярный кислый белок) и Nf-L (neurofilament light chain -легкие цепи нейрофиламентов) -индикаторов реактивного астроглиоза, возникаю щего при развитии нейровоспаления в головном мозге и сыворотке крови до и после лечения [59].…”

Section: применение ноотропов и нейропротекторов для коррекции додеме...unclassified

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Pathogenetic mechanisms of cognitive impairment in cerebrovascular pathology and prospects for their correction using nootropic and neuroprotective agents

Smirnova¹,

Zhivolupov

2023

Medicinskij sovet

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The article presents modern ideas about the pathogenesis of cognitive disorders in cerebrovascular pathology at the cellular level. Dysfunction of neurovascular units is associated with impaired microcirculation, hypoxia, deficiency of energy resources, development of neuroinflammation, increased nitric oxide synthesis and oxidative stress, glutamate excitotoxicity, intracellular calcium accumulation, endothelial dysfunction, impaired circulation of cerebrovascular fluid, venous outflow from the cranial cavity and utilization of brain metabolic products, including misshaped proteins. The above determines the possibility of the combined development of cerebrovascular and neurodegenerative diseases, primarily Alzheimer’s disease. Currently, mixed (vascularneurodegenerative) brain damage is considered as the main cause of cognitive disorders, which is confirmed by the data of post-mortem studies. Pathogenetic therapy of dementia with cholinesterase inhibitors and memantine does not eliminate the cognitive defect, but only slows down its progression. The impossibility of restoring the premorbid level of daily activity of the patient in the treatment of cognitive impairment at the stage of dementia dictates the need for the use of adjuvant nootropic and neuroprotective agents until the breakdown of the functional reserve, that is, at the stage of moderate cognitive impairment. Nicotinoyl gamma-aminobutyric acid has nootropic, tranquilizing, psychostimulant and antioxidant properties. Studies of the last decade have proven the ability of nicotinoyl gamma-aminobutyric acid to suppress neuroinflammation and apoptosis of cells of the central nervous system, increase the expression of angiogenic and cytoskeletal proteins, normalize the permeability of the blood-brain barrier, which can be used to improve the function of neurovascular units and correct vascular-neurodegenerative cognitive impairment. A small number of drug interactions with nicotinoyl gamma-aminobutyric acid allows it to be included in the complex therapy of comorbid patients.

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Carotenoids and Vitamins of Pollen

Mărgăoan,

Cornea-Cipcigan

2023

Pollen Chemistry &Amp; Biotechnology

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Modulatory effects of vitamin B3 and its derivative on the levels of apoptotic and vascular regulators and cytoskeletal proteins in diabetic rat brain as signs of neuroprotection

Cited by 8 publications

References 57 publications

Benzodiazepine receptor agonist carbacetam modulates the level of vascular endothelial growth factor in the retina of rats with streptozotocin-induced diabetes

Benzodiazepine receptor agonist carbacetam modulates the level of vascular endothelial growth factor in the retina of rats with streptozotocin-induced diabetes

Pathogenetic mechanisms of cognitive impairment in cerebrovascular pathology and prospects for their correction using nootropic and neuroprotective agents

Carotenoids and Vitamins of Pollen

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