Ameliorative Effects of α-Tocopherol and/or Coenzyme Q10 on Phenytoin-Induced Cognitive Impairment in Rats: Role of VEGF and BDNF-TrkB-CREB Pathway

Nagib, Marwa M.; Tadros, Mariane G.; Rahmo, Rania M.; Sabri, Nagwa Ali; Khalifa, Amani E.; Masoud, Somaia I.

doi:10.1007/s12640-018-9971-6

Cited by 21 publications

(10 citation statements)

References 87 publications

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“…Furthermore, the protective effects of citicoline, vitamin B3 and CAVAQ10 ® were also corroborated by their efficacy in inhibiting the hydrogen peroxide-induced up-regulation of both IL-6 and TNFα. These results indicated an important anti-neuroinflammatory effect of this association, which seems to be crucial to contain the neuronal loss in some NDs [ 39 ]. This could also suggest the ability of the tested formula in limiting and/or partially preventing the burdens of inflammation and oxidative stress that occur in chronic inflammatory disorders, including glaucoma.…”

Section: Discussionmentioning

confidence: 99%

Citicoline/Coenzyme Q10/Vitamin B3 Fixed Combination Exerts Synergistic Protective Effects on Neuronal Cells Exposed to Oxidative Stress

et al. 2022

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Background: The present study aimed to investigate the rationale and efficacy of using a citicoline, coenzyme Q10 (CAVAQ10) and vitamin B3 fixed combination in combating inflammation and oxidation in neuronal cells exposed to oxidative stress. Methods: HypoE22 cells and isolated hypothalamic specimens were selected as in vitro models to conduct the experiments. The efficacy of citicoline, CAVAQ10, and vitamin B3, with their fixed combination, were assayed after the exposure of hypothalamic cells to hydrogen peroxide (concentration range 1 nM–10 µM), in order to evaluate the biocompatibility of treatments. The activity of neuroprotective and pro-inflammatory factors, namely, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα), involved in the neuronal cell damage in neurodegenerative diseases, were assayed in isolated hypothalamus. Results: Neither citicoline, CAVAQ10, nor vitamin B3 significantly altered hypothalamic cell viability, thus suggesting the biocompatibility of single ingredients and fixed combination in the concentration range considered for the study. In the same condition, citicoline and CAVAQ10 were also effective in reducing the gene expression of monoaminoxidase-B, involved in dopamine degradation. However, only citicoline demonstrated an ability to reduce dopamine levels. Conversely, all compounds were effective in reducing the gene expression of IL-6, and TNFα, and in inducing the gene expression of BDNF, with the co-administration of citicoline/CAVAQ10/vitamin B3 being generally more effective than single ingredients. Conclusions: The present findings support the beneficial and synergistic effects of citicoline, CAVAQ10, and vitamin B3 in fixed combination in reducing inflammation and oxidation, and in stimulating neurotrophin production in neuronal cells.

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Section: Discussionmentioning

confidence: 99%

Citicoline/Coenzyme Q10/Vitamin B3 Fixed Combination Exerts Synergistic Protective Effects on Neuronal Cells Exposed to Oxidative Stress

et al. 2022

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“…BDNF is involved in learning ability and memory processes, and is also a critical molecule for neuroprotection [26,27]. BDNF and VEGF play an important role in restoring cognitive function and memory loss due to brain damage [28]. The present study showed that in human neuronal SH-SY5Y cells, the expression of BDNF and VEGF decreased after LPS and sevoflurane exposure for the environmental induction of POCD.…”

Section: Discussionmentioning

confidence: 56%

Effect of Polydeoxyribonucleotide on Lipopolysaccharide and Sevoflurane-Induced Postoperative Cognitive dysfunction in Human Neuronal SH-SY5Y Cells

Jeong¹,

Chung²,

Ko³

et al. 2019

Int Neurourol J

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Postoperative cognitive dysfunction (POCD) is a complication of surgery characterized by acute cognitive dysfunction, memory impairment, and loss of attention. The effect of polydeoxyribonucleotide (PDRN) on the POCD environment induced by lipopolysaccharide (LPS) and sevoflurane exposure were investigated in human neuronal SH-SY5Y cells. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and WST-8 assays were performed to determine cell viability. Cyclic adenosine-3,5′-monophosphate (cAMP), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 concentrations were measured using enzyme-linked immunoassay (ELISA). Immunocytochemistry was performed for vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF), and western blotting for TNF-α, IL-1β, IL-6, and cAMP response element-binding protein (CREB). Results: Induction of the POCD environment reduced cell viability in the MTT and WST-8 assays. PDRN treatment reduced TNF-α, IL-1β, and IL-6 expression in POCD conditions, and significantly increased cAMP concentrations and the p-CREB/ CREB ratio. PDRN treatment activated adenosine A2A receptors and then increased the expression of VEGF and BDNF, which had been reduced by LPS and sevoflurane exposure. Conclusions: PDRN treatment showed a therapeutic effect on the LPS and sevoflurane-induced POCD environment. PDRN was shown to have an excellent therapeutic effect on POCD, not only by promoting rapid anti-inflammatory effects in damaged cells, but also by enhancing the expression of BDNF and VEGF.

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“…CoQ10 has been found to be a safe and effective adjuvant for AED therapy in epilepsy rodent models, suggesting that it could ameliorate seizure severity and protect against seizure-induced oxidative damage causing cognitive impairment associated with chronic use of AEDs [ 10 , 34 ]. The possible underlying molecular mechanism by which CoQ10 alleviates phenytoin-induced cognitive impairment is related to VEGF and enhances the BDNF-TrkB-CREB signaling pathway in the hippocampus and cortex of phenytoin-treated rats [ 35 ]. In addition, CoQ10 showed antiseizure activity through the induction of constitutive nitric oxide synthase expression in pentylenetetrazole or electroshock-induced mouse models [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Association between the Serum Coenzyme Q10 Level and Seizure Control in Patients with Drug-Resistant Epilepsy

et al. 2021

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Drug-resistant epilepsy (DRE) is a chronic neurological disorder with somatic impacts and increased risk of metabolic comorbidities. Oxidative stress might play an important role in metabolic effects and as a regulator of seizure control, while coenzyme Q10 (CoQ10) could improve insulin sensitivity through antioxidant effects. We aimed to investigate the association between CoQ10 level and clinical outcome, represented by the seizure frequency and quality of life, in DRE patients. DRE patients (N = 33) had significantly higher serum insulin levels and lower scores on the physical domain of the World Health Organization Quality of Life questionnaire (WHOQoL) than gender-age matched controls. The serum CoQ10 level (2910.4 ± 1163.7 ng/mL) was much higher in DRE patients than the normal range. Moreover, the serum CoQ10 level was significantly correlated with the seizure frequency (r = −0.412, p = 0.037) and insulin level (r = 0.409, p = 0.038). Based on stratification by insulin resistance (HOMA-IR > 2.4), the subgroup analysis showed that patients with a greater HOMA-IR had higher CoQ10 levels and lower seizure frequency, and had a significantly worse quality of life. In summary, CoQ10 could be a mediator involved in the mechanism of epilepsy and serve as a biomarker of the clinical outcome in DER patients.

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Ameliorative Effects of α-Tocopherol and/or Coenzyme Q10 on Phenytoin-Induced Cognitive Impairment in Rats: Role of VEGF and BDNF-TrkB-CREB Pathway

Cited by 21 publications

References 87 publications

Citicoline/Coenzyme Q10/Vitamin B3 Fixed Combination Exerts Synergistic Protective Effects on Neuronal Cells Exposed to Oxidative Stress

Citicoline/Coenzyme Q10/Vitamin B3 Fixed Combination Exerts Synergistic Protective Effects on Neuronal Cells Exposed to Oxidative Stress

Effect of Polydeoxyribonucleotide on Lipopolysaccharide and Sevoflurane-Induced Postoperative Cognitive dysfunction in Human Neuronal SH-SY5Y Cells

Association between the Serum Coenzyme Q10 Level and Seizure Control in Patients with Drug-Resistant Epilepsy

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