Monthly Archives: August 2020

Antioxidant Effect Of Vitamin E On Carbon Tetrachloride Induced Tubulointerstitial And Glomerular Damage In The Kidneys Of Albino Mice

Shabnum Aamir, Zia Ud Din, Zahid Sarfaraz Khan, Humaira Imtiaz, Faheem Ul Haq, Hajira Ishaq

J Ayub Med Coll Abbottabad . Jul-Sep 2020;32(3):295-298.

Abstract

Background: Chemical induced nephrotoxicity is one of the main causes of acute kidney injury. The objective of this study was to determine the antioxidant effect of vitamin E against carbon tetrachloride induced tubulointerstitial and glomerular damage in the kidney of albino mice.

Methods: The study had been conducted on albino mice. The duration of study was for five weeks. A total of 35 animals were randomly divided into five groups A, B, C, D and E .The group A served as control group, group B was administered only with carbon tetrachloride (no vitamin E) and groups C, D and E received test drug (vitamin E) in doses of 1, 10 and 50mg/kg body weight respectively along with CCl4. The animals were dissected and kidneys were excised for microscopic study for possible histo-morphological effects.

Results: It was observed that carbon tetrachloride treated experimental groups developed tubulo-interstitial and glomerular changes as compared to control group A. The results suggested that these changes were significantly reduced in vitamin E treated groups especially in dose of 50 mg/kg body weight.

Conclusions: This study reveals that tubulointerstitial and glomerular damage caused by carbon tetrachloride can be reduced by vitamin E in dose of 50 mg/kg body weight.

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Effects of pomegranate peel extract and vitamin E on the inflammatory status and endothelial function in hemodialysis patients: a randomized controlled clinical trial

Tina Jafari, Aziz A Fallah, Ali Reyhanian, Elham Sarmast

Food Funct . 2020 Aug 25. doi: 10.1039/d0fo01012j. Online ahead of print.

Abstract

Inflammation and endothelial dysfunction are major problems in hemodialysis (HD) patients. This study assessed the effects of an 8 week administration of pomegranate peel extract (PPE) and vitamin E (Vit E) alone or in combination on the biomarkers of inflammation, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and the biomarkers of endothelial function, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin, in HD patients. In a randomized, double-blind, parallel, placebo-controlled trial, 100 HD patients were randomly divided into 4 equal groups: (a) PPE + Vit E, received 2 pomegranate tablets (each tablet contained 225 mg PPE, equal to 90 mg ellagic acid) + 1 Vit E soft gel (400 IU) daily, (b) PPE, received 2 pomegranate tablets + 1 Vit E placebo soft gel daily, (c) Vit E, received 1 Vit E soft gel + 2 pomegranate placebo tablets daily, and (d) placebo, received 2 pomegranate placebo tablets + 1 Vit E placebo soft gel daily. For group allocation, a stratified block randomization procedure based on sex, age, and HD duration was used. Each intervention product and its placebo had identical shape, color, size, and packaging. Consumption of PPE + Vit E significantly reduced the serum CRP level (mean change: -7.12 ± 4.59 mg l-1, P < 0.001) compared to other groups, while reduced levels of IL-6 (mean change: -2.19 ± 2.33 pg ml-1, P < 0.001), TNF-α (mean change: -2.41 ± 3.21 pg ml-1, P = 0.008), ICAM-1 (mean change: -64.2 ± 111.0 ng ml-1, P = 0.017), and VCAM-1 (mean change: -117.7 ± 177.1 ng ml-1, P = 0.002) were observed compared to the control. There was no significant difference in the P-selectin level among the groups. Consumption of PPE or Vit E alone significantly reduced the CRP level (mean change for PPE: -3.58 ± 5.41 mg l-1, P < 0.001; mean change for Vit E: -3.25 ± 8.29 mg l-1, P = 0.002) compared to the control. As a result, consumption of PPE in combination with Vit E enhanced the inflammatory status and endothelial function in HD patients.

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Brain tocopherol levels are associated with lower activated microglia density in elderly human cortex

Francisca A de Leeuw, Julie A Schneider, Sonal Agrawal, Sue E Leurgans, Martha Clare Morris

Alzheimers Dement (N Y) . 2020 Aug 24;6(1):e12021. doi: 10.1002/trc2.12021. eCollection 2020.

Abstract

Introduction: Higher brain tocopherol levels have been associated with lower levels of Alzheimer’s disease (AD) neuropathology; however, the underlying mechanisms are unclear.

Methods: We studied the relations of α- and γ-tocopherol brain levels to microglia density in 113 deceased participants from the Memory and Aging Project. We used linear regression analyses to examine associations between tocopherol levels and microglia densities in a basic model adjusted for age, sex, education, apolipoprotein E (APOE)ε4 genotype (any ε4 allele vs. none) , and post-mortem time interval, and a second model additionally adjusted for total amyloid load and neurofibrillary tangle severity.

Results: Higher α- and γ-tocopherol levels were associated with lower total and activated microglia density in cortical but not in subcortical brain regions. The association between cortical α-tocopherol and total microglia density remained statistically significant after adjusting for AD neuropathology.

Discussion: These results suggest that the relation between tocopherols and AD might be partly explained by the alleviating effects of tocopherols on microglia activation.

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A vitamin E blended highly cross-linked polyethylene acetabular cup results in less wear: 6-year results of a randomized controlled trial in 199 patients

Julie R A Massier, Joost H J Van Erp, Thom E Snijders, Arthur DE Gast

Acta Orthop . 2020 Aug 24;1-6. doi: 10.1080/17453674.2020.1807220. Online ahead of print.

Abstract

Background and purpose – Survivorship of total hip arthroplasty (THA) with the ultra-high molecular weight polyethylene (UHMWPE) monoblock cup has been limited due to periprosthetic osteolysis and aseptic loosening, secondary to wear of the UHMWPE. In response, a vitamin E blended highly cross-linked polyethylene (HXLPE) cup was developed. This study set out to compare the wear and clinical 6-year outcomes of vitamin E blended HXLPE with UHMWPE in an isoelastic monoblock cup in patients with hip osteoarthritis who underwent uncemented THA. The 2-year results have been reported previously.Patients and methods – For this randomized controlled trial 199 patients were included. 102 patients received the vitamin E blended HXLPE uncemented acetabular cup and 97 patients the uncemented UHMWPE monoblock cup. Clinical and radiographic parameters were obtained preoperatively, directly postoperatively, and at 3, 12, 24, and 72 months. Wear rates were compared using the femoral head penetration (FHP) rate.Results – 173 patients (87%) completed the 6-year follow-up. The mean NRS scores for rest pain, load pain, and patient satisfaction were 0.3 (SD 1), 0.6 (SD 1), and 8.6 (SD 1) respectively. The mean Harris Hip Score was 93 (SD 12). The FHP rate was lower in the vitamin E blended HXLPE cup (0.028 mm/year) compared with the UHMWPE cup (0.035 mm/year) (p = 0.002). No adverse reactions associated with the clinical application of vitamin E blended HXLPE were observed. 15 complications occurred, equally distributed between the two cups. The 6-year survival to revision rate was 98% for both cups. There was no aseptic loosening.Interpretation – This study shows the superior performance of the HXLPE blended with vitamin E acetabular cup with clinical and radiographic results similar to the UHMWPE acetabular cup.

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Dose-Dependent Pulmonary Toxicity of Aerosolized Vitamin E Acetate

Shotaro Matsumoto, Xiaohui Fang , Maret G Traber, Kirk D Jones, Charles Langelier, Paula Hayakawa Serpa, Carolyn S Calfee, Michael A Matthay, Jeffrey E Gotts

Am J Respir Cell Mol Biol . 2020 Aug 21. doi: 10.1165/rcmb.2020-0209OC. Online ahead of print.

Abstract

E-cigarette, or vaping, product use-associated lung injury (EVALI) is a syndrome of acute respiratory failure characterized by monocytic and neutrophilic alveolar inflammation. Epidemiological and clinical evidence suggests a role of Vitamin E acetate (VEA) in the development of EVALI, yet it remains unclear whether VEA has direct pulmonary toxicity. To test the hypotheses that aerosolized VEA causes lung injury in mice and directly injures human alveolar epithelial cells, we exposed adult mice and primary human alveolar epithelial type II (AT II) cells to an aerosol of VEA generated by a device designed for vaping oils. Outcome measures in mice included lung edema, bronchoalveolar lavage (BAL) analysis, histology, and inflammatory cytokines; in vitro outcomes included cell death, cytokine release, cellular uptake of VEA, and gene expression analysis. Comparison exposures in both models included the popular nicotine-containing JUUL aerosol. We discovered that VEA caused dose-dependent increases in lung water and BAL protein compared to control and JUUL-exposed mice in association with increased BAL neutrophils, oil-laden macrophages, multinucleated giant cells, and inflammatory cytokines. VEA aerosol was also toxic to AT II cells, causing increased cell death and the release of monocyte and neutrophil chemokines. VEA was directly absorbed by AT II cells, resulting in the differential gene expression of several inflammatory biological pathways. Given the epidemiological and clinical characteristics of the EVALI outbreak, these results suggest that VEA plays an important causal role.

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Gamma-Tocotrienol loaded liposomes as radioprotection from hematopoietic side effects caused by radiotherapeutic drugs

Sang-Gyu Lee, Teja Muralidhar Kalidindi, Hanzhi Lou, Kishore Gangangari, Blesida Punzalan, Ariana Bitton 2, Casey Lee, Soobin Park, Lisa Bodei, Michael Kharas, Vijay K Singh, NagaVaraKishore Pillarsetty, Steven M Larson

J Nucl Med . 2020 Aug 21;jnumed.120.244681. doi: 10.2967/jnumed.120.244681. Online ahead of print.

Abstract

Rationale: With the successful development and increased use of targeted radionuclide therapy for treating cancer comes the increased risk of radiation injury to bone marrow-both direct suppression and stochastic effects, leading to neoplasia. Herein, we report a novel radioprotector drug, a liposomal formulation of gamma-tocotrienol (GT3), or GT3-Nano for short, to mitigate bone marrow radiation damage during targeted radionuclide therapy (TRT). Methods: GT3 was loaded into liposomes using passive loading. [64Cu]-GT3-Nano and 3H-GT3-Nano were synthesized to study the in vivo biodistribution profile of the liposome and GT3 individually. Radioprotection efficacy of GT3-Nano was assessed after acute 137Cs whole-body irradiation at sublethal (4 Gy), lethal (9 Gy), or single high-dose [153Sm]-EDTMP administration. Flow cytometry was used to analyze hematopoietic cell population dynamics and fluorescence microscopy was used to assess the cellular site of GT3-Nano localization in the spleen and bone marrow. Results: Bone marrow uptake and retention of [64Cu]-GT3-Nano was 6.98 ± 2.34 %ID/g, while [3H]-GT3-Nano uptake and retention was 7.44 ± 2.52 %ID/g at 24 h, respectively. GT3-Nano administered 24 hours before or after 4 Gy TBI promoted rapid and complete hematopoietic recovery while recovery of controls stalled at 60%. GT3-Nano demonstrated dose-dependent radioprotection, achieving 90% survival at 50 mg/kg against lethal 9 Gy TBI. Flow cytometry of bone marrow indicated progenitor bone marrow cells MPP2 and CMP cells were upregulated in GT3-Nano-treated mice. Immunohistochemistry showed that GT3-Nano accumulates in CD105-positive sinusoid epithelial cells. Conclusion: GT3-Nano is highly effective in mitigating marrow suppressive effects of sub-lethal and lethal TBI in mice. GT3-Nano can aid in rapid recovery of hematopoietic components in mice treated with the endoradiotherapeutic agent [153Sm]-EDTMP.

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Protective effect of hypothermia and vitamin E on spermatogenic function after reduction of testicular torsion in rats

Xuejun Bo, Ping Wang, Yan Nie, Rongfen Li, Jiru Lu, Haiying Wang

Exp Ther Med . 2020 Aug;20(2):796-801. doi: 10.3892/etm.2020.8800. Epub 2020 May 27.

Abstract

This study was designed to investigate the protective effect of hypothermia and vitamin E on spermatogenic function after reduction of testicular torsion in rats. Ninety-six pure inbred male SD rats were divided into group A, B, C and D according to the principle of body weight and birth similarity, with 24 rats in each group. Four groups of rats were respectively twisted on the left testis to establish unilateral testicular torsion rats. Rats in groups A, B, C, D were respectively given normal saline, hypothermia therapy, vitamin E therapy, and hypothermia and vitamin E therapy. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of the four groups were detected, and the correlation levels of inflammatory factors IL-1β, hs-CRP and related sex hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T) were detected by ELISA. Apoptosis of spermatogenic cells of testis in the four groups was detected by flow cytometry. SOD activity and MDA content in groups B, C and D were significantly higher than those in group A, MDA content was significantly lower than that in group A (P<0.05), SOD activity in group D was higher than that in groups B and C, while MDA content was lower than that in groups B and C (P<0.05). The levels of IL-1β and hs-CRP in group A were much higher than those in groups B, C and D (P<0.05). LH and FSH levels in group A were significantly higher than those in groups B, C and D (P<0.05), and in group D were significantly lower than those in groups B and C (P<0.05). Apoptosis rate of spermatogenic cells in group A was significantly higher than that in groups B, C and D (P<0.05). Hypothermia combined with vitamin E can reverse testicular injury in rats and reduce the apoptosis rate of spermatogenic cells.

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The wonders of palm oil

The Malaysian Palm Oil Board (MPOB)’s research and collaborations with local and overseas institutions have scientifically proven that palm-derived Vitamin E tocotrienols are important for human health as they can prevent many non-communicable diseases.Through the continuous and dedicated research conducted by MPOB, the health benefits of palm oil and its phyto-nutrients are being explored extensively.

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Systematic review with meta-analysis: The effect of vitamin E supplementation in adult patients with non-alcoholic fatty liver disease

Andreas Vadarlis, Christina Antza, Dimitra Rafailia Bakaloudi, Ioannis Doundoulakis, Georgios Kalopitas, Myrto Samara, Theodoros Dardavessis, Theofanis Maris, Michael Chourdakis

J Gastroenterol Hepatol . 2020 Aug 18. doi: 10.1111/jgh.15221. Online ahead of print.

Abstract

Background: Νon-alcoholic fatty liver disease (NAFLD) is estimated to be the most common cause of end-stage liver disease in the next years. Vitamin E has shown beneficial effects as a possible “scavenger” of oxidative stress products, which play a major role in pathogenesis of the disease.

Aims: The purpose of the present meta-analysis is to investigate the effects of vitamin E supplementation in biochemical and histological parameters in adult patients with NAFLD.

Methods: Literature search was performed in major electronic databases (MEDLINE, CENTRAL and EMBASE) up to June 2020 for randomized clinical trials, which examined vitamin E versus placebo treatment in adults with NAFLD. Changes in liver enzymes were considered as primary outcomes, while changes in histology, biochemical and metabolic parameters as secondary. Quality of evidence was assessed through risk of bias according to the Cochrane risk of bias tool.

Results: Eight studies were included in qualitative analysis and seven in quantitative analysis. Vitamin E reduced the values of liver enzymes compared to placebo (-7.37 IU/L, 95% CI: -10.11 to -4.64 for ALT and -5.71 IU/L, 95% CI: -9.49 to -1.93 for AST) Additionally, vitamin E improved statistically significantly liver pathology in every individual histologic parameter as well LDL, FBG and serum leptin values.

Conclusions: Vitamin E can improve biochemical and histological characteristics of NAFLD patients, especially of NASH patients. The results indicate that vitamin E could be a promising choice and be considered as a treatment option in patients with NAFLD.

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Synergistic Impact of Xanthorrhizol and d-δ-Tocotrienol on the Proliferation of Murine B16 Melanoma Cells and Human DU145 Prostate Carcinoma Cells

Darren Chan, Maureen L Meister, Chappell R Madhani, Manal Elfakhani, Sophie T Yount, Xiangming Ji, Rafaela G Feresin, Desiree Wanders, Huanbiao Mo

Nutr Cancer . 2020 Aug 18;1-12. doi: 10.1080/01635581.2020.1807573. Online ahead of print

Abstract

Isoprenoids suppress the mevalonate pathway that provides prenyl groups for the posttranslational modification of growth-regulating proteins. We hypothesize that xanthorrhizol and d-δ-tocotrienol synergistically suppress the growth of murine B16 melanoma and human DU145 prostate carcinoma cells. Xanthorrhizol (0-200 µmol/L; half maximal inhibitory concentration [IC50] = 65 µmol/L) and d-δ-tocotrienol (0-40 µmol/L; IC50 = 20 µmol/L) each induced a concentration-dependent suppression of the proliferation of B16 cells and concurrent cell cycle arrest at the G1 phase. A blend of 16.25 µmol/L xanthorrhizol and 10 µmol/L d-δ-tocotrienol suppressed B16 cell proliferation by 69%, an impact greater than the sum of those induced by xanthorrhizol (15%) and d-δ-tocotrienol (12%) individually. The blend cumulatively reduced the levels of cyclin-dependent kinase four and cyclin D1, key regulators of cell cycle progression at the G1 phase. The expression of RAS and extracellular signal-regulated kinase (ERK1/2) in the proliferation-stimulating RAS-RAF-MEK-ERK pathway was downregulated by the blend. Xanthorrhizol also induced a concentration-dependent suppression of the proliferation of DU145 cells with concomitant morphological changes. Isobologram confirmed the synergistic effect of xanthorrhizol and d-δ-tocotrienol on DU145 cell proliferation with combination index values ranging 0.61-0.94. Novel combinations of isoprenoids with synergistic actions may offer effective approaches in cancer prevention and therapy.

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