Exploring the effect of vitamin E in cancer chemotherapy-A biochemical and biophysical insight

Bhori M, Singh K, Marar T, Chilakapati MK

J Biophotonics. 2018 Sep;11(9):e201800104. doi: 10.1002/jbio.201800104. Epub 2018 Jun 8.

Abstract

Many oncologists contend that patient undergoing chemotherapy must avoid antioxidant supplementation as it may interfere with the activity of the drug. In the present investigation, we have explored the influence of vitamin E, a well-known antioxidant on Camptothecin (CPT), a potent anti-cancer drug induced cell apoptosis and death of cervical cancer cells. HeLa cells were treated with different concentrations of CPT in presence and absence of 100 μm vitamin E. Treated cells were subjected to cytotoxicity studies, catalase assay, DNA fragmentation assay, clonogenic assay and flow cytometry based apoptosis detection. Also, Raman spectroscopy a label free technique which provides global information, in conjunction with multivariate tools like PCA, PCLDA and FDA, was investigated to explore vitamin E supplementation induced alterations. Our data based on biochemical and biophysical experimental analysis reveals that CPT causes DNA damage along with protein and lipid alteration culminating in cell death. Importantly, Raman spectroscopic analysis could uniquely differentiate the cluster of control and vitamin E control from CPT and CPT + Vit E treated cells. We conclusively prove that presence of vitamin E at 100 μM concentration shows promising antioxidant activity and displays no modulatory role on CPT induced effect, thereby causing no possible hindrance with the efficacy of the drug. Vitamin E may prove beneficial to alleviate chemotherapy associated side effects in patients during clinical settings which may open the doors further for subsequent exploration in in vivo preclinical studies.

Cuerq C, Henin E, Restier L, Blond E, Drai J, Marçais C, Di Filippo M, Laveille C, Michalski MC, Poinsot P, Caussy C, Sassolas A, Moulin P, Reboul E, Charriere S, Levy E, Lachaux A, Peretti N

J Lipid Res. 2018 Sep;59(9):1640-1648. doi: 10.1194/jlr.M085043. Epub 2018 Jul 18.

Abstract

Abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) are extremely rare recessive forms of hypobetalipoproteinemia characterized by intestinal lipid malabsorption and severe vitamin E deficiency. Vitamin E is often supplemented in the form of fat-soluble vitamin E acetate, but fat malabsorption considerably limits correction of the deficiency. In this crossover study, we administered two different forms of vitamin E, tocofersolan (a water-soluble derivative of RRR-α-tocopherol) and α-tocopherol acetate, to three patients with ABL and four patients with CMRD. The aims of this study were to evaluate the intestinal absorption characteristics of tocofersolan versus α-tocopherolacetate by measuring the plasma concentrations of α-tocopherol over time after a single oral load and to compare efficacy by evaluating the ability of each formulation to restore vitamin E storage after 4 months of treatment. In patients with ABL, tocofersolan and α-tocopherolacetate bioavailabilities were extremely low (2.8% and 3.1%, respectively). In contrast, bioavailabilities were higher in patients with CMRD (tocofersolan, 24.7%; α-tocopherol acetate, 11.4%). Plasma concentrations of α-tocopherol at 4 months were not significantly different by formulation type in ABL or CMRD. This study provides new insights about vitamin E status in ABL and CMRD and suggests the potential of different formulations as treatment options.

Sapiejka E, Krzyżanowska-Jankowska P, Wenska-Chyży E, Szczepanik M, Walkowiak D, Cofta S, Pogorzelski A, Skorupa W, Walkowiak J

Adv Med Sci. 2018 Sep;63(2):341-346. doi: 10.1016/j.advms.2018.04.001. Epub 2018 Aug 3.

Abstract

PURPOSE:

The risk of vitamin E deficiency is of primary concern in cystic fibrosis patients. However, early diagnosis and routine vitamin Esupplementation can lead to its normal or even high levels. In the present study, we assessed vitamin E status in a large group of cystic fibrosis patients. Moreover, we also aimed to establish determinants of its body resources in cystic fibrosis patients.

MATERIAL AND METHODS:

The study group comprised 211 cystic fibrosis patients aged from 1 month to 48 years. In all of them serum α-tocopherol concentration was analyzed using high-performance liquid chromatography.

RESULTS:

Median vitamin E concentration was 9.9 μg/ml (1st-3rd quartile: 7.5-13.5). Vitamin E deficiency was found in 17 (8.0%) and high levels were documented in 24 (11.4%) participants. Patients with and without vitamin E deficiency did not differ significantly with respect to age, standardized body weight and height, FEV1, albumin concentration and vitamin E supplementation dose. However, vitamin E deficiency appeared more frequently in participants without vitamin E supplementation. Moreover, in multiple linear regression analysis pancreatic insufficiency, severe CFTR gene mutation and vitamin E dose, were potentially defined as determinants of vitamin E concentration.

CONCLUSIONS:

Vitamin E deficiency in cystic fibrosis patients is rather rare nowadays. Excessive vitamin E levels seem to be more frequent. Vitamin E status wasn’t documented to be strictly related to clinical determinants. Beyond vitamin E supplementation, exocrine pancreatic function and CFTR gene mutations may have had an impact on the vitamin E body resources in cystic fibrosis patients.

Dai W, Qi C, Wang S

Biomed Pharmacother. 2018 Sep;105:835-840. doi: 10.1016/j.biopha.2018.05.136. Epub 2018 Jun 18.

Abstract

The effect of glucosamine and vitamin E against rheumatoid arthritis (RA) in a neonatal rat model was investigated. Lipid peroxidation, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), glutathione peroxidase (Gpx), matrix metalloproteinase-3 (MMP-3), prostaglandin E₂ (PGE₂), ceruloplasmin, copper, zinc, nitric oxide (NO), uric acid, inducible nitric oxide synthase (iNOS), and nuclear factor-kappaB (NF-κB) levels were determined in control and rheumatoid arthritis neonatal rats. Glucosamine plus vitamin E supplementation reduced the MDA level by 61.9% and increased the SOD, catalase, GSH, Gpx, and zinc levels. MMP-3, PGE₂, ceruloplasmin, copper, NO and uric acid levels were significantly reduced by supplementation of glucosamine plus vitamin E. NF-κB, and iNOS protein levels were decreased by 47.7% and 39.5%, respectively, by glucosamine plus vitamin E supplementation. Thus, supplementation with glucosamine plus vitamin E exerted a synergistic effect against RA.

Singh J, Kaur K, Kumar P

J Food Sci Technol. 2018 Sep;55(9):3625-3631. doi: 10.1007/s13197-018-3288-6. Epub 2018 Jul 11.

Abstract

α–Tocopherol is a well-known fat-soluble antioxidant and is widely used in the food industry for stabilizing free radicals. Incorporation and stability of it into food is another challenge as directly added α–tocopherol is prone to inactivation by food constituents. This study was aimed at optimizing conditions for encapsulation of α–tocopherol using combination of sodium alginate (0.5, 1.0, 1.5 and 2.0%) as primary wall material and pectin (2.0%) as filler. The optimum conditions were selected on the basis of encapsulation efficiency, shape, size, bulk density, yield and swelling index with syringe method. The encapsulation efficiency of α–tocopherol in microencapsules produced under optimal conditions was 52.91% using sodium alginate 1.5% w/v and pectin 2.0% w/v. α–Tocopherol was encapsulated with encapsulator using standard conditions and was compared with syringe method. The encapsulation efficiency was found more (55.97%) in microencapsules prepared with encapsulator and 52.11% in microencapsules prepared with syringe.

Mune M, Uto-Kondo H, Iteya I, Fujii Y, Ikeda S, Ikewaki K

Clin Nephrol. 2018 Sep;90(3):212-221. doi: 10.5414/CN109197.

Abstract

BACKGROUND AND AIMS:

Patients with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) have been shown to be at increased risk for cardiovascular disease (CVD). Decreased high-density lipoprotein cholesterol (HDL-C) and impaired cholesterol efflux capacity (CEC) have been reported in such patients, and effects of vitamin E supplementation on HDL functions are poorly understood. Therefore, the present study aimed to investigate effects of vitamin E supplementation on HDL and endothelial functions in ESKD patients undergoing HD. We also assessed the influence of diabetes and haptoglobin (Hp) phenotype on the effects of vitamin E.

MATERIALS AND METHODS:

Vitamin E (300 mg daily) was supplemented for 12 weeks, followed by a 10-week washout phase in 40 ESKD patients undergoing HD (20 diabetic and 20 nondiabetic patients). HDL functions, including CEC, antioxidant capacity, and anti-inflammatory activity, were investigated. In diabetic patients, endothelial function, as represented by flow-mediated vasodilatation (FMD), was also assessed. The findings were compared according to diabetic condition or Hp phenotype.

RESULTS:

Vitamin E significantly increased CEC, whereas antioxidant capacity and anti-inflammatory activity remained unchanged. Further, the improvement in CEC was maintained after the 10-week washout phase. Endothelial function was significantly improved in diabetic patients. Subanalyses based on diabetes or Hp phenotype revealed that neither diabetes nor Hp phenotype influenced the effects of vitamin E.

CONCLUSION:

In ESKD patients undergoing hemodialysis, vitamin E supplementation significantly improved the HDL function of CEC and, in diabetic patients, endothelial function. These effects were independent of Hp phenotype.

Meydani SN, Lewis ED, Wu D

Adv Nutr. 2018 Sep 1;9(5):533-543. doi: 10.1093/advances/nmy035.

Abstract

Current vitamin E requirements are uniformly applied across the population for those >14 y of age. However, aging is associated with alterations in cellular and physiologic functions, which are affected by vitamin E. Therefore, it is questionable whether vitamin E requirements can be uniformly applied to all adult age categories. With aging, there is dysregulation of the immune system in which there are decreased cell-mediated and pathogen defense responses coupled with an overactive, prolonged inflammatory state. Both animal and human studies in the aged suggest that intake above currently recommended levels of vitamin E may improve immune and inflammatory responses and be associated with a reduced risk of infectious disease. We review the evidence that was considered in establishing the current requirements for vitamin E and highlight data that should be considered in determining the vitamin E requirements in older adults, particularly focusing on the evidence suggesting a benefit of increased vitamin E intake on immune function and inflammatory processes and resistance to infection. The main objective of this Perspective is to initiate the discussion of whether the current Dietary Reference Intake for vitamin E should be increased for the older population. We make this suggestion on the basis of mechanistic studies showing biological plausibility, correction of a major cellular dysfunction in older adults, and strong evidence from several animal and a few human studies indicating a reduction in risk and morbidity from infections.

Abdulla KA, Um CY, Gross MD, Bostick RM

J Nutr. 2018 Sep 1;148(9):1453-1461. doi: 10.1093/jn/nxy132.

Abstract

BACKGROUND:

Although α- and γ-tocopherol are co-consumed antioxidants, circulating γ-tocopherol concentrations were paradoxically found to be inversely associated with total vitamin E intake and circulating α-tocopherol concentrations. There are limited data on this apparent paradox or on determinants of circulating γ-tocopherol concentrations.

OBJECTIVE:

To help clarify possible determinants of circulating γ-tocopherol concentrations, we investigated associations of circulating γ-tocopherol concentrations with various dietary and lifestyle factors and biomarkers of oxidative stress and inflammation.

METHODS:

We pooled cross-sectional data from 2 outpatient, adult, elective colonoscopy populations (pooled n = 419) on whom extensive dietary, lifestyle, and medical information was collected, and the following plasma concentrations were measured: α- and γ-tocopherol (via HPLC), F2-isoprostanes (FiPs; via gas chromatography-mass spectrometry), and high-sensitivity C-reactive protein (hsCRP; via latex-enhanced immunonephelometry). Multivariable general linear models were used to assess mean γ-tocopherol differences across quantiles of plasma antioxidant micronutrients, FiPs, and hsCRP; an oxidative balance score [OBS; a composite of anti- and pro-oxidant dietary and lifestyle exposures (a higher score indicates higher antioxidant relative to pro-oxidant exposures)]; and multiple dietary and lifestyle factors.

RESULTS:

Adjusted for serum total cholesterol, mean γ-tocopherol concentrations among those in the highest relative to the lowest tertiles of circulating α-tocopherol and β-carotene, the OBS, and total calcium and dietary fiber intakes were 31.0% (P < 0.0001), 29.0% (P < 0.0001), 27.6% (P = 0.0001), 29.7% (P < 0.0001), and 18.6% (P = 0.008) lower, respectively. For those in the highest relative to the lowest tertiles of circulating FiPs and hsCRP, mean γ-tocopherol concentrations were 50% (P < 0.0001) and 39.0% (P < 0.0001) higher, respectively.

CONCLUSIONS:

These findings support the conclusion that circulating γ-tocopherol concentrations are inversely associated with antioxidant exposures and directly associated with systemic oxidative stress and inflammation in adults. Additional research on possible mechanisms underlying these findings and on whether circulating γ-tocopherol may serve as a biomarker of oxidative stress, inflammation, or both is needed.

Bhatti SA, Khan MZ, Hassan ZU, Saleemi MK, Khatoon A, Abidin ZU, Hameed MR

Toxicon. 2018 Aug 29. pii: S0041-0101(18)30358-1. doi: 10.1016/j.toxicon.2018.08.012. [Epub ahead of print]

Abstract

This study aimed to evaluate the effect of dietary ochratoxin A (OA), in the presence and absence of L-carnitine (LC) and vitamin E (VE), on the humoral immune responses of White Leghorn cockerels (WLC). One-day old white male Leghorn chicks were divided into 12 groups, having 20 birds each and were offered ration contaminated with OA (1.0 or 2.0 mg/kg feed) alone and concurrently with LC (1.0 g/kg) and/or VE (0.2 g/kg), for 42 days. The humoral immune responses were accessed by lymphoproliferative response to avian tuberculin, in-vivo phagosomes activity to carbon particles and antibody response to the sheep red blood cells (SRBCs). The dietary addition of OA alone suppressed the humoral immune responses, however, the exposure of birds to 1.0 mg/kg OA in the presence of LC and/or VE showed a significant reduction in OA induced immunotoxicity. This protective response was absent in the birds fed 2.0 mg/kg OA in the presence and absence of LC and/or VE. Histopathological and morphometric examination of the bursa of Fabricius exhibited a decrease in the severity and frequency of OA induced lesions in the presence of dietary LC and/or VE. The use of LC and VE as dietary supplement, can effectively overcome OA (≤1.0 mg/kg) induced immunosuppression.

Mukai K, Ishikawa E, Ouchi A, Nagaoka SI, Abe K, Suzuki T, Izumisawa K

Lipids. 2018 Aug 28. doi: 10.1002/lipd.12053. [Epub ahead of print]

Abstract

Recently, a new assay method that can quantify the singlet oxygen-absorption capacity (SOAC) of antioxidants (AO) and food extracts in homogeneous organic solvents has been proposed. In the present study, second-order rate constants (k_Q ) for the reaction of singlet oxygen (¹ O₂ ) with vitamin E homologs (α-, β-, γ-, and δ-tocopherols [Toc] and α-, β-, γ-, and δ-tocotrienols [Toc-3]) were measured in an aqueous Triton X-100 (5.0 wt%) micellar solution (pH 7.4). Toc-3 showed k_Q values larger than those of Toc in a micellar solution, although Toc and Toc-3 showed the same k_Q values in a homogeneous solution. Similar measurements were performed for 5 palm oil extracts 1-5 and one soybean extract 6, which contained different concentrations of Toc, Toc-3, and carotenoids. It has been clarified that the ¹ O₂ -quenching rates (k_Q ) (that is, the relative SOAC value) obtained for extracts 3-6 may be explained as the sum of the product ΣkQAO-iAO-i/100 of the rate constant (kQAO-i) and the concentration ([AO-i]/100) of AO-i contained. The UV-vis absorption spectra of Toc and Toc-3 were measured in a micellar solution and chloroform. The results obtained demonstrated that the k_Q values of AO in homogeneous and heterogeneous solutions vary notably depending on (1) polarity (dielectric constant [ε]) of the reaction field between ¹ O₂ and AO, (2) the local concentration of AO, and (3) the mobility of AO in solution. The results suggest that the SOAC method is applicable to the measurement of ¹ O₂ -quenching activity of general food extracts in a heterogeneous micellar solution.