Vitamin E Prevents ΔN-Bcl-xL-associate Mitochondrial Dysfunction in Primary Hippocampal Neurons (P14-024-19)

Park HA, Mnatsakanyan N, Broman K, Jonas E

Curr Dev Nutr. 2019 Jun 13;3(Suppl 1). pii: nzz052.P14-024-19. doi: 10.1093/cdn/nzz052.P14-024-19. eCollection 2019 Jun.

Abstract

OBJECTIVES:

B-cell lymphoma-extra large (Bcl-xL) is a pro-survival protein localized to mitochondria. Bcl-xL is reported to support brain function by enhancing neuronal energy metabolism, synapse formation, and neurite outgrowth. However, under exposure to excitotoxic stimulation and subsequent oxidative stress, Bcl-xL undergoes caspase dependent cleavage to ∆N-Bcl-xL. Accumulation of ∆N-Bcl-xL is associated with neuronal death; thus, approaches that prevent ∆N-Bcl-xL accumulation protect neurons from excitotoxic insult. In this study, we hypothesize that ∆N-Bcl-xL formation is regulated by redox status in mitochondria. We thus tested if production of ∆N-Bcl-xL can be inhibited by the fat-soluble antioxidant α-tocotrienol (TCT) given its ability to scavenge free radicals produced in the mitochondrial membrane.

METHODS:

Primary hippocampal neurons were treated with α-TCT, glutamate, or a combination of both, and mitochondrial oxidative stress, mitochondrial potential, caspase activity, and ∆N-Bcl-xL protein levels were quantified.

RESULTS:

Glutamate caused abnormalities in mitochondrial function leading to neuronal death. The antioxidant α-TCT protected neurons from glutamate-induced mitochondrial dysfunction and cytotoxicity. α-TCT treatment protected against cleavage of full length anti-apoptotic Bcl-xL to form pro-death ∆N-Bcl-xL. α-TCT significantly attenuated glutamate-induced reactive oxygen species (ROS) formation, caspase 3 activation and ∆N-Bcl-xL formation at mitochondria.

CONCLUSIONS:

Our data suggests that oxidative stress production during excitotoxicity is responsible for the formation of ∆N-Bcl-xL. Thus, application of a lipophilic antioxidant such as vitamin E is neuroprotective by improving mitochondrial redox status and preventing production of neurotoxic ∆N-Bcl-xL.

Domosławska A, Zduńczyk S, Janowski T

J Vet Res. 2019 Jun 12;63(2):293-297. doi: 10.2478/jvetres-2019-0025. eCollection 2019 Jun.

Abstract

INTRODUCTION:

Significant improvement of sperm motility within one month effected by oral supplementation of selenium and vitamin E was described in four infertile male dogs which failed to conceive in their last three matings with different bitches.

MATERIAL AND METHODS:

The dogs (a Golden Retriever, an English Cocker Spaniel, and two Tibetan Mastiffs) were supplemented daily with selenium (Se) (0.6 mg/kg organic Se yeast) and vitamin E (vit. E) (5 mg/kg) per os for 60 days. Semen was collected on days 0, 30, 60, and 90. The sperm concentration and motility parameters were evaluated by the CASA system, sperm morphology was explored by Diff-Quick staining, and live and dead spermatozoa were differentiated by eosin/nigrosin staining. The concentrations of Se and vit. E were measured in peripheral blood serum on semen collection days.

RESULTS:

Before administration, the concentrations of Se in blood plasma were low (86.0-165.0 μg/L). After 30 days of treatment there was an observable improvement in total and progressive sperm motility and kinematic parameters (VAP, VSK, VCL, ALH, BCF, and RAPID). The percentages of live and normal morphology sperm cells were also higher. There was also an observable increase in Se and vitamin Econcentrations in blood serum. Bitches were successfully mated and delivered four to six puppies.

CONCLUSION:

Supplementation with Se and vit. E improved rapid sperm motility and restored fertility in infertile dogs with low Se status.

Shamsi Meymandi M, Sepehri G, Izadi G, Zamiri Z

Pharmacol Rep. 2019 Jun;71(3):457-464. doi: 10.1016/j.pharep.2019.02.005. Epub 2019 Feb 12.

Abstract

BACKGROUND:

The aim of this study was to evaluate the effect of vitamin E co-administration with celecoxib in thermal and inflammatory pain in two model of pain assessment including thermal tail flick test of acute pain and formalin induced inflammatory model in adult male rats.

METHODS:

Seventy two male Wistar rats were divided into a vehicle received intraperitoneally olive oil, indomethacin (20 mg/kg), vitamin E(100, 200 and 400 mg/kg), celecoxib (3, 10, 30 and 60 mg/kg) groups, and combination groups received the combination of vitamin E (100 and 200 mg/kg) and celecoxib (3, 10 and 30 mg/kg). All drugs were dissolved in olive oil. Antinociceptive effect in tail-flick was measured using Area Under Curve (AUC) of responses and Maximum Possible Effect (%MPE) and pain score was used for antinociceptive response in formalin test.

RESULTS:

Vitamin E and celecoxib changed time course of pain scores in a dose related manner in formalin test but not in tail-flick test. Vitamin E (200 mg/kg) had no effect and merely 60 mg/kg of celecoxib increased %MPE and AUC in tail-flick. The combination of vitamin E(100 or 200 mg/kg) with celecoxib (3 or 10 mg/kg) decreased pain scores compared to vehicle in both phases of formalin test, while in chronic phase (II) the pain scores of combination groups were also decreased compared to vitamin E and celecoxib. However, in tail-flick test the combination of ineffective doses of vitamin E (200 mg/kg) and celecoxib (10 and 30 mg/kg) increased %MPE and AUC compared to vehicle but not compared to celecoxib or vitamin E.

CONCLUSIONS:

Vitamin E and celecoxib showed a dose related antinociceptive effect in inflammatory but not in thermal model of acute pain. However the co-administration of vitamin E with celecoxib caused a significant increase in the antinociceptive effect which was similar to indomethacin, as a standard anti-inflammatory drug. So we suggest the concomitant use of vitamin E with celecoxib and other NSAIDs for potentiation of both anti- inflammatory and analgesic response, as well as the reduction of cardiovascular side effects of celecoxib.

Harper RA, Petersen L, Saleh MM, Proctor GB, Carpenter GH, Gambogi R, Hider R, Jones SA

Nanomedicine. 2019 Jun 11;21:102010. doi: 10.1016/j.nano.2019.04.013. [Epub ahead of print]

Abstract

The phosphorylation of (+) alpha tocopherol produces adhesive nanostructures that interact with oral biofilms to restrict their growth. The aim of this work was to understand if these adhesive (+) alpha tocopheryl phosphate (α-TP) nanostructures could also control macrophage responses to the presence of oral bacteria. The (+) α-TP planar bilayer fragments (175 nm ± 21 nm) formed in a Trizma®/ethanol vehicle swelled when exposed to the cell lines (maximum stabilized size = 29 μm). The swelled (+) α-TP aggregates showed selective toxicity towards THP-1 macrophages (LD₅₀ = 304 μM) compared to human gingival fibroblasts (HGF-1 cells; LD₅₀ > 5 mM), and they inhibited heat killed bacteria stimulated MCP-1 production in both macrophages (control 57.3 ± 18.1 pg/mL vs (+) α-TP 6.5 ± 3.2 pg/mL) and HGF-1 cells (control 673.5 ± 133 pg/mL vs (+) α-TP – 463.9 ± 68.9 pg/mL).

Qu YH, Jian LY, Ce L, Ma Y, Xu CC, Gao YF, Machaty Z, Luo HL

Anim Reprod Sci. 2019 Jun;205:52-61. doi: 10.1016/j.anireprosci.2019.04.003. Epub 2019 Apr 10.

Abstract

Dietary vitamin E supplementation is beneficial to semen quality in different sheep and goat breeds. The aim of this research was to further investigate the effect of vitamin E in sheep on spermatogenesis and its regulatory mechanisms using RNA-seq. Thirty male Hu lambs were randomly divided into three groups. The animals received 0, 200 or 2000 IU/day vitamin E dietary supplementation for 105 days, and its effects were subsequently evaluated. The results indicate vitamin E supplementation increased the number of germ cells in the testes and epididymides. The positive effects were reduced, however, in animals that received 2000 IU/d vitamin E. Using the RNA-seq procedure, there was detection of a number of differentially expressed genes such as NDRG1, FSCN3 and CYP26B1 with these genes being mainly related to the regulation of spermatogenesis. Supplementation with 2000 IU/d vitamin E supplementation resulted in a lesser abundance of skeleton-related transcripts such as TUBB, VIM and different subtypes of collagen, and there was also an effect on the ECM-receptor interaction pathway. These changes appear to be responsible for the lesser beneficial effect of the greater vitamin E concentrations. The results provide a novel insight into the regulation of spermatogenesis by vitamin E at the molecular level, however, for a precise understanding of functions of the affected genes there needs to be further study.

Hassan WN, Bin-Jaliah I, Haidara MA, Eid RA, Heidar EHA, Dallak M, Al-Ani B

Ultrastruct Pathol. 2019 Jun 9:1-9. doi: 10.1080/01913123.2019.1627446. [Epub ahead of print]

Abstract

We recently reported an animal model of osteoarthritis (OA) induced by a combination of the chondrocyte glycolysis inhibitor, monoiodoacetate (MIA) and the agent that induces diabetes mellitus, streptozotocin (STZ). Here we investigated the potential protective effect of the antioxidant and anti-inflammatory agent, vitamin E against MIA+STZ-induced OA. Therefore, rats were either injected once with MIA (2 mg/50 μL) + 65 mg/kg STZ before being sacrificed after 8 weeks (model group) or were treated immediately after MIA+STZ injections with vitamin E (600 mg/kg; thrice a week) before being sacrificed after 8 weeks (treatment group). Using scanning and transmission electron microscopy examinations, we observed in the model group a substantial damage to the articular cartilage of the knee joint as demonstrated by the destruction of the chondrocytes, territorial matrix, disrupted lacunae, collagen fibers, and profound chondrocyte ultrastructural alterations such as degenerated chondrocyte, irregular cytoplasmic membrane, damaged mitochondria and rough endoplasmic reticulum, vacuolated cytoplasm, presence of lipid droplets and different sizes of lysosomes, which were substantially but not completely protected by vitamin E. H&E stained sections of knee joint articular cartilage showed that MIA+STZ induced damage to the chondrocyte and territorial matrix. Vitamin E also significantly (p < .05) inhibited MIA+STZ-induced blood levels of the inflammatory biomarkers, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) that are known to be modulated in OA and diabetes. We conclude that vitamin E protects against MIA+STZ-induced knee joints injuries in rats, which is associated with the inhibition of biomarkers of inflammation.

Shamsi Meymandi M, Sepehri G, Izadi G, Zamiri Z

Pharmacol Rep. 2019 Jun;71(3):457-464. doi: 10.1016/j.pharep.2019.02.005. Epub 2019 Feb 12.

Abstract

BACKGROUND:

METHODS:

RESULTS:

CONCLUSIONS:

Rozanowska M, Edge R, Land EJ, Navaratnam S, Sarna T, Truscott TG

Int J Mol Sci. 2019 Jun 7;20(11). pii: E2799. doi: 10.3390/ijms20112799.

Abstract

Retinoids are present in human tissues exposed to light and under increased risk of oxidative stress, such as the retina and skin. Retinoid cation radicals can be formed as a result of the interaction between retinoids and other radicals or photoexcitation with light. It has been shown that such semi-oxidized retinoids can oxidize certain amino acids and proteins, and that α-tocopherol can scavenge the cation radicals of retinol and retinoic acid. The aim of this study was to determine (i) whether β-, γ-, and δ-tocopherols can also scavenge these radicals, and (ii) whether tocopherols can scavenge the cation radicals of another form of vitamin A-retinal. The retinoid cation radicals were generated by the pulse radiolysis of benzene or aqueous solution in the presence of a selected retinoid under oxidizing conditions, and the kinetics of retinoid cation radical decays were measured in the absence and presence of different tocopherols, Trolox or urate. The bimolecular rate constants are the highest for the scavenging of cation radicals of retinal, (7 to 8) × 10⁹ M^-1·s^-1, followed by retinoic acid, (0.03 to 5.6) × 10⁹M^-1·s^-1, and retinol, (0.08 to 1.6) × 10⁸ M^-1·s^-1. Delta-tocopherol is the least effective scavenger of semi-oxidized retinol and retinoic acid. The hydrophilic analogue of α-tocopherol, Trolox, is substantially less efficient at scavenging retinoid cation radicals than α-tocopherol and urate, but it is more efficient at scavenging the cation radicals of retinoic acid and retinol than δ-tocopherol. The scavenging rate constants indicate that tocopherols can effectively compete with amino acids and proteins for retinoid cation radicals, thereby protecting these important biomolecules from oxidation. Our results provide another mechanism by which tocopherols can diminish the oxidative damage to the skin and retina and thereby protect from skin photosensitivity and the development and/or progression of changes in blinding retinal diseases such as Stargardt’s disease and age-related macular degeneration (AMD).

Moradi A, Ziamajidi N, Ghafourikhosroshahi A, Abbasalipourkabir R

Mol Biol Rep. 2019 Jun;46(3):2919-2932. doi: 10.1007/s11033-019-04752-4. Epub 2019 Mar 18.

Abstract

The increasing application of titanium dioxide nanoparticles (NTiO₂) in life and the toxicity potential of these nanoparticles have raised concerns about their detrimental effects on human health. This study was conducted to investigate the hepatoprotective effects of vitamin Eand vitamin A against hepatotoxicity induced by NTiO₂ in rats. Thirty-six male Wistar rats were randomly divided into six groups of six rats each. Intoxicated group received 300 mg/kg NTiO₂ for two weeks by gavage. Groups treated with vitamin E (100 IU/kg), vitamin A (100 IU/kg) and mixture of these vitamins were orally administered for 3 weeks (started 7 days before NTiO₂ administration). In order to investigate the redox changes, total antioxidant capacity, total oxidant status, and lipid peroxidation were determined in liver tissue as well as activity of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and catalase. In addition, inflammatory responses were assessed by measuring the expression of NF-κB (mRNA) and TNF-α (mRNA and protein). Histopathological analysis and measurement of liver enzymes (ALP, ALT, AST, and LDH in serum) were also done to determine hepatic injury. In liver, NTiO₂ caused hepatic injury, redox perturbation, and reduction of antioxidant enzymes and elevation of inflammatory mediators, significantly. However, treatment with vitamins was able to significantly ameliorate these alterations. This study highlights the antioxidant and anti-inflammatory properties of vitamins A and E against toxicity of NTiO₂ and poses the use of these vitamins to mitigate the toxic effects of this nanoparticles in NTiO₂-contained products.

Ilesanmi-Oyelere BL, Brough L, Coad J, Roy N, Kruger MC

Nutrients. 2019 Jun 3;11(6). pii: E1262. doi: 10.3390/nu11061262.

Abstract

In women, the menopausal transition is characterized by acid-base imbalance, estrogen deficiency and rapid bone loss. Research into nutritional factors that influence bone health is therefore necessary. In this study, the relationship between nutrient patterns and nutrients important for bone health with bone mineral density (BMD) was explored. In this cross-sectional analysis, 101 participants aged between 54 and 81 years were eligible. Body composition and BMD analyses were performed using dual-energy X-ray absorptiometry (DXA). Nutrient data were extracted from a 3-day diet diary (3-DDD) using Foodworks 9 and metabolic equivalent (MET-minutes) was calculated from a self-reported New Zealand physical activity questionnaire (NZPAQ). Significant positive correlations were found between intakes of calcium (p = 0.003, r = 0.294), protein (p = 0.013, r = 0.246), riboflavin (p = 0.020, r = 0.232), niacin equivalent (p = 0.010, r = 0.256) and spine BMD. A nutrient pattern high in riboflavin, phosphorus and calcium was significantly positively correlated with spine (p < 0.05, r = 0.197) and femoral neck BMD (p < 0.05, r = 0.213), while the nutrient pattern high in vitamin E, α-tocopherol, β-carotene and omega 6 fatty acids was negatively correlated with hip (p < 0.05, r = -0.215) and trochanter BMD (p < 0.05, r = -0.251). These findings support the hypothesis that a nutrient pattern high in the intake of vitamin E, α-tocopherol and omega 6 fatty acids appears to be detrimental for bone health in postmenopausal women.