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 MM, Tadros MG, Rahmo RM, Sabri NA, Khalifa AE, Masoud SI

Neurotox Res. 2018 Oct 29. doi: 10.1007/s12640-018-9971-6. [Epub ahead of print]

Abstract

Phenytoin is one of the most well-known antiepileptic drugs that cause cognitive impairment which is closely related to cAMP response element-binding protein (CREB) brain-derived neurotrophic factor (BDNF) signaling pathway. Moreover, vascular endothelial growth factor (VEGF), an endothelial growth factor, has a documented role in neurogenesis and neuronal survival and cognitive impairment. Therefore, this study aimed to investigate the influence of powerful antioxidants: α-Toc and CoQ10 alone or combined in the preservation of brain tissues and the maintenance of memory formation in phenytoin-induced cognitive impairment in rats. The following behavioral test novel object recognition and elevated plus maze were assessed after 14 days of treatment. Moreover, VEGF, BDNF, TrkB, and CREB gene expression levels in the hippocampus and prefrontal cortex were estimated using RT-PCR. Both α-Toc and CoQ10 alone or combined with phenytoin showed improvement in behavioral tests compared to phenytoin. Mechanistically, α-Toc and/or CoQ10 decreases the VEGF mRNA expression, while increases BDNF-TrKB-CREB mRNA levels in hippocampus and cortex of phenytoin-treated rats. Collectively, α-Toc and/or CoQ10 alleviated the phenytoin-induced cognitive impairment through suppressing oxidative damage. The underlying molecular mechanism of the treating compounds is related to the VEGF and enhancing BDNF-TrkB-CREB signaling pathway. Our study indicated the usefulness α-Toc or CoQ10 as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress.

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VE-Albumin Core-Shell Nanoparticles for Paclitaxel Delivery to Treat MDR Breast Cancer

Tang B, Qian Y, Gou Y, Cheng G, Fang G

Molecules. 2018 Oct 25;23(11). pii: E2760. doi: 10.3390/molecules23112760.

Abstract

Multi-drug resistance (MDR) presents a serious problem in cancer chemotherapy. In this study, Vitamin E (VE)-Albumin core-shell nanoparticles were developed for paclitaxel (PTX) delivery to improve the chemotherapy efficacy in an MDR breast cancer model. The PTX-loaded VE-Albumin core-shell nanoparticles (PTX-VE NPs) had small particle sizes (about 100 nm), high drug entrapment efficiency (95.7%) and loading capacity (12.5%), and showed sustained release profiles, in vitro. Docking studies indicated that the hydrophobic interaction and hydrogen bonds play a significant role in the formation of the PTX-VE NPs. The results of confocal laser scanning microscopy analysis demonstrated that the cell uptake of PTX was significantly increased by the PTX-VE NPs, compared with the NPs without VE (PTX NPs). The PTX-VE NPs also exhibited stronger cytotoxicity, compared with PTX NPs with an increased accumulation of PTX in the MCF-7/ADR cells. Importantly, the PTX-VE NPs showed a higher anti-cancer efficacy in MCF-7/ADR tumor xenograft model than the PTX NPs and the PTX solutions. Overall, the VE-Albumin core-shell nanoparticles could be a promising nanocarrier for PTX delivery to improve the chemotherapeutic efficacy of MDR cancer.

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Inhibition of Osteocyte Membrane Repair Activity via Dietary Vitamin E Deprivation Impairs Osteocyte Survival

Hagan ML, Bahraini A, Pierce JL, Bass SM, Yu K, Elsayed R, Elsalanty M, Johnson MH, McNeil A, McNeil PL, McGee-Lawrence ME

Calcif Tissue Int. 2018 Oct 24. doi: 10.1007/s00223-018-0487-0. [Epub ahead of print]

Abstract

Osteocytes experience plasma membrane disruptions (PMD) that initiate mechanotransduction both in vitro and in vivo in response to mechanical loading, suggesting that osteocytes use PMD to sense and adapt to mechanical stimuli. PMD repair is crucial for cell survival; antioxidants (e.g., alpha-tocopherol, also known as Vitamin E) promote repair while reactive oxygen species (ROS), which can accumulate during exercise, inhibit repair. The goal of this study was to determine whether depleting Vitamin E in the diet would impact osteocyte survival and bone adaptation with loading. Male CD-1 mice (3 weeks old) were fed either a regular diet (RD) or Vitamin E-deficient diet (VEDD) for up to 11 weeks. Mice from each dietary group either served as sedentary controls with normal cage activity, or were subjected to treadmill exercise (one bout of exercise or daily exercise for 5 weeks). VEDD-fed mice showed more PMD-affected osteocytes (+ 50%) after a single exercise bout suggesting impaired PMD repair following Vitamin E deprivation. After 5 weeks of daily exercise, VEDD mice failed to show an exercise-induced increase in osteocyte PMD formation, and showed signs of increased osteocytic oxidative stress and impaired osteocyte survival. Surprisingly, exercise-induced increases in cortical bone formation rate were only significant for VEDD-fed mice. This result may be consistent with previous studies in skeletal muscle, where myocyte PMD repair failure (e.g., with muscular dystrophy) initially triggers hypertrophy but later leads to widespread degeneration. In vitro, mechanically wounded MLO-Y4 cells displayed increased post-wounding necrosis (+ 40-fold) in the presence of H2O2, which could be prevented by Vitamin E pre-treatment. Taken together, our data support the idea that antioxidant-influenced osteocyte membrane repair is a vital aspect of bone mechanosensation in the osteocytic control of PMD-driven bone adaptation.

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Familial Dysautonomia Affects Jews Almost Exclusively

Familial dysautonomia (FD) ; also known as Riley-Day syndrome and autonomic neuropathy type III, is a genetic disorder that affects the development and survival of certain nerve cells and causes sensory and autonomic dysfunction. The autonomic nervous system controls involuntary actions such as digestion, breathing, production of tears and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat and cold.

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Inhibition of Osteocyte Membrane Repair Activity via Dietary Vitamin E Deprivation Impairs Osteocyte Survival

Hagan ML1, Bahraini A, Pierce JL, Bass SM1, Yu K, Elsayed R, Elsalanty M, Johnson MH3, McNeil A, McNeil PL, McGee-Lawrence ME

Calcif Tissue Int. 2018 Oct 24. doi: 10.1007/s00223-018-0487-0. [Epub ahead of print]

Abstract

Osteocytes experience plasma membrane disruptions (PMD) that initiate mechanotransduction both in vitro and in vivo in response to mechanical loading, suggesting that osteocytes use PMD to sense and adapt to mechanical stimuli. PMD repair is crucial for cell survival; antioxidants (e.g., alpha-tocopherol, also known as Vitamin E) promote repair while reactive oxygen species (ROS), which can accumulate during exercise, inhibit repair. The goal of this study was to determine whether depleting Vitamin E in the diet would impact osteocyte survival and bone adaptation with loading. Male CD-1 mice (3 weeks old) were fed either a regular diet (RD) or Vitamin E-deficient diet (VEDD) for up to 11 weeks. Mice from each dietary group either served as sedentary controls with normal cage activity, or were subjected to treadmill exercise (one bout of exercise or daily exercise for 5 weeks). VEDD-fed mice showed more PMD-affected osteocytes (+ 50%) after a single exercise bout suggesting impaired PMD repair following Vitamin E deprivation. After 5 weeks of daily exercise, VEDD mice failed to show an exercise-induced increase in osteocyte PMD formation, and showed signs of increased osteocytic oxidative stress and impaired osteocyte survival. Surprisingly, exercise-induced increases in cortical bone formation rate were only significant for VEDD-fed mice. This result may be consistent with previous studies in skeletal muscle, where myocyte PMD repair failure (e.g., with muscular dystrophy) initially triggers hypertrophy but later leads to widespread degeneration. In vitro, mechanically wounded MLO-Y4 cells displayed increased post-wounding necrosis (+ 40-fold) in the presence of H2O2, which could be prevented by Vitamin E pre-treatment. Taken together, our data support the idea that antioxidant-influenced osteocyte membrane repair is a vital aspect of bone mechanosensation in the osteocytic control of PMD-driven bone adaptation.

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Synergistic potential of propolis and vitamin E against sub-acute toxicity of AlCl3 in Albino mice: in vivo study

Sajjad S, Malik H, Saeed L, Hashim I, Farooq U, Manzoor F

Physiol Res. 2018 Oct 23. [Epub ahead of print]

Abstract

Current study evaluated the synergistic potential of propolis and Vitamin E against sublethal toxicity of aluminum chloride on different biochemical parameters and liver histology. Swiss albino mice (n=42) were randomly divided into five groups. Group I received 0.2 ml of 0.9 % saline solution, Group II received Propolis (50 mg/kg b.w.), Group III received Vitamin E (150 mg/kg b.w.), Group IV received AlCl3 50 mg/kg b.w., Group V received AlCl3 + Propolis, Group VI received AlCl3 + Vitamin E and Group VI received AlCl3 + propolis + Vitamin E. Blood and tissue samples were collected after 7 and 21 days. The body weight of the animals significantly increased in all groups except group IV. The concentration of serum high density lipoprotein significantly decreased in group IV and increased in group V, VI and VII. The level of aspartate aminotransferase, alanine transferase, alkaline phosphatase, triglycerides, total cholesterol, and low density lipoprotein significantly increased in AlCl3 treated group and increased in group V, VI and VII. Tissue sections were processed and stained by hematoxylin and eosin. Group II showed cellular necrosis. Group V, VI showed decreased number of vacuolization, sinusoidal spacing and macrophage cell infiltration. Group VI showed less degenerative changes in the third week. Vitamin E and propolis in combination with Al provides more protection against AlCl3 induced toxicity.

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Neurobiological Correlates of Alpha-Tocopherol Antiepileptogenic Effects and MicroRNA Expression Modulation in a Rat Model of Kainate-Induced Seizures

Ambrogini P, Albertini MC, Betti M, Galati C, Lattanzi D, Savelli D, Di Palma M, Saccomanno S, Bartolini D, Torquato P, Ruffolo G, Olivieri F, Galli F, Palma E, Minelli A, Cuppini R

Mol Neurobiol. 2018 Oct;55(10):7822-7838. doi: 10.1007/s12035-018-0946-7. Epub 2018 Feb 22.

Abstract

Seizure-triggered maladaptive neural plasticity and neuroinflammation occur during the latent period as a key underlying event in epilepsy chronicization. Previously, we showed that α-tocopherol (α-T) reduces hippocampal neuroglial activation and neurodegeneration in the rat model of kainic acid (KA)-induced status epilepticus (SE). These findings allowed us to postulate an antiepileptogenic potential for α-T in hippocampal excitotoxicity, in line with clinical evidence showing that α-T improves seizure control in drug-resistant patients. To explore neurobiological correlates of the α-T antiepileptogenic role, rats were injected with such vitamin during the latent period starting right after KA-induced SE, and the effects on circuitry excitability, neuroinflammation, neuronal death, and microRNA (miRNA) expression were investigated in the hippocampus. Results show that in α-T-treated epileptic rats, (1) the number of population spikes elicited by pyramidal neurons, as well as the latency to the onset of epileptiform-like network activity recover to control levels; (2) neuronal death is almost prevented; (3) down-regulation of claudin, a blood-brain barrier protein, is fully reversed; (4) neuroinflammation processes are quenched (as indicated by the decrease of TNF-α, IL-1β, GFAP, IBA-1, and increase of IL-6); (5) miR-146a, miR-124, and miR-126 expression is coherently modulated in hippocampus and serum by α-T. These findings support the potential of a timely intervention with α-T in clinical management of SE to reduce epileptogenesis, thus preventing chronic epilepsy development. In addition, we suggest that the analysis of miRNA levels in serum could provide clinicians with a tool to evaluate disease evolution and the efficacy of α-T therapy in SE.

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Comparison of the Effects of Omega 3 and Vitamin E on Palcitaxel-Induced Peripheral Neuropathy

Anoushirvani AA, Poorsaadat L, Aghabozorgi R, Kasravi M

Open Access Maced J Med Sci. 2018 Oct 21;6(10):1857-1861. doi: 10.3889/oamjms.2018.333. eCollection 2018 Oct 25.

Abstract

BACKGROUND:

Paclitaxel-induced peripheral neuropathy is the most important side effect limiting the use of this medication.

AIM:

This study aimed to compare the effects of omega-3 and vitamin E on the incidence of peripheral neuropathy in patients receiving Taxol.

METHODS:

In this clinical trial, 63 patients who were a candidate for receiving taxol, were enrolled based on inclusion and exclusion criteria. In group O, patients received 640 mg omega-3 three times a day, and group E, received 300 mg vitamin E two times a day. Patients took the supplements up to three months after the onset of Taxol. Group P received placebo for a similar period. All patients referred to a neurologist for electrophysiological evaluation before the onset of chemotherapy and at months 1 and 3. The presence of neuropathy and its progression was recorded by the neurologist.

RESULTS:

Neurological examination in this study indicated that 6 patients (28.6%) in Group O, 7 patients (33.3%) in group E, and 15 patients (71.4%) in placebo group started peripheral neuropathy. There was a significant difference between intervention groups and the placebo group (p = 0.0001) and no significant difference between intervention groups (p = 0.751).

CONCLUSION:

Our data suggested that vitamin E and omega-3 may significantly reduce the incidence of Paclitaxel-induced peripheral neuropathy. Routine administration of such supplements that have no special side effect for patients under chemotherapy may greatly enhance their quality of life.

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Hepatoprotective effects of vitamin E against hexachlorobenzene-induced hepatotoxicity and oxidative stress in rats: histological, biochimical and antioxidant status changes

Chalouati H, Ben Sâad MM, Payrastre L

Toxicol Mech Methods. 2018 Oct 3:1-8. doi: 10.1080/15376516.2018.1506847. [Epub ahead of print]

Abstract

The protective effects of α-Tocopherol (vitamin E) on liver injury induced by hexachlorobenzene (HCB) were investigated in adult male rats of Wistar strain. Animals were randomly divided into six groups of eight rats each. Group 1 and 2 have received HCB, dissolved in olive oil, at a dose of 4 mg or 16 mg/kg b.w., respectively. Group 3 and 4 were treated by the same doses of HCB (4 mg and 16 mg/kg b.w.) after 1 h of pretreatment with α-tocopherol at a dose of 100 mg kg-1 b.w. The other two groups served as controls; which received either olive oil only, a solvent of HCB, or α-tocopherol. A significant increase in hepatic lipid peroxidation (LPO) and GSH activity were observed following HCB administration. The activities of antioxidant enzymes like superoxide dismutase and catalase were significantly decreased while glutathione peroxidase was significantly increased following HCB administration. Similarly, a significant increase in plasma levels of various marker enzymes [aminotransferase (aspartate aminotransférase (AST) and alanine aminotransferase (ALT)), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)] and a decrease of total protein level were observed. Pretreatment with vitamin E of HCB treated rats ameliorated all biochemical parameters to near normal values. Liver histological study confirmed biochemical parameters and the beneficial role of vitamin E.

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