E-cigarette or Vaping Product Use-Associated Lung Injury

Philip W Ind

Br J Hosp Med (Lond) . 2020 Apr 2;81(4):1-9. doi: 10.12968/hmed.2019.0371.

Abstract

E-cigarette or vaping product use-associated lung injury is a recently recognised, acute pulmonary syndrome which has been reported (particularly from June to October 2019) throughout the USA, but not in Europe (although one probable case, in the UK, has been reported; Medicines and Healthcare products Regulatory Agency, 2020). It presents acutely, most often in young men, as severe pulmonary consolidation, usually with respiratory failure. The mortality is around 2%. The cause(s) are unknown, but it is associated with vaping, particularly using unlicensed cannabis-containing products with tetrahydrocannabinol. Vitamin E acetate, often present in tetrahydrocannabinol-containing vape products as a solvent, has been implicated, as it has been identified in the bronchoalveolar lavage fluid of patients with e-cigarette or vaping product use-associated lung injury. This article reviews the recent literature, including clinical features, presentation and investigations, and possible mechanisms, in the context of vaping practices in the USA and the UK.

Veen L, Hantikainen E, Bellocco R, Ye W, Serafini M, Ponzano M, Grotta A, Trolle Lagerros Y

Eur J Nutr. 2020 Apr 2. doi: 10.1007/s00394-020-02239-8. [Epub ahead of print]

Abstract

PURPOSE:

Oxidative stress might play an important role in the development of osteoarthritis, but not much is known about the effect of antioxidants on osteoarthritis risk. We, therefore, aimed to investigate the effect of dietary vitamin C, E, beta-carotene, and non-enzymatic antioxidant capacity (NEAC), which measures overall antioxidant activity from the diet, on the risk of osteoarthritis.

METHODS:

For this study 43,865 men and women from the Swedish National March Cohort (SNMC) were followed for up to 19 years. We computed dietary intake of vitamin C, E and beta-carotene using information from a Food Frequency Questionnaire (FFQ). To estimate dietary NEAC we combined the information from the FFQ with food item-specific antioxidant capacity values from an antioxidant food database. Cases of osteoarthritis were identified through the Swedish National Patient Registers. We categorized all exposure variables into sex-specific quartiles and used multivariable-adjusted Cox proportional hazards regression models to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs).

RESULTS:

In total, we observed 5976 cases of OA during 469,148 person-years of follow-up. After adjusting for potential confounders, we did not find any association between vitamin C, beta-carotene and NEAC (p-values for trend > 0.5), but a positive association was found with higher dietary vitamin E intake (HR Q4 vs Q1: 1.11; 95% CI 1.02-1.21; p for trend = 0.01) and the risk of OA.

CONCLUSION:

Our findings do not provide evidence for dietary antioxidants to protect from the development of OA, and a higher dietary vitamin E intake might even increase the risk.

Zhang D, Wang B, Sun Y, Wang C, Mukherjee S, Yang C, Chen Y

Macromol Biosci. 2020 Apr 2:e2000036. doi: 10.1002/mabi.202000036. [Epub ahead of print]

Abstract

Burn wound healing remains a challenging health problem worldwide due to the lack of efficient and precise therapy. Inherent oxidative stress following burn injury is importantly responsible for prolonged inflammation, fibrotic scar, and multiple organ failure. Herein, a bioinspired antioxidative defense system coupling with in situ forming hydrogel, namely, multiresponsive injectable catechol-Fe³⁺ coordination hydrogel (MICH) matrix, is engineered to promote burn-wound dermal repair by inhibiting tissue oxidative stress. This MICH matrix serves as the special traits of “Fe-superoxide dismutases,” small molecular antioxidant (vitamin E), and extracellular matrix (ECM) in alleviating cellular oxidative damage, which demonstrates precise scavenging on reactive oxygen species (ROS) of different cellular locations, blocking lipid peroxidation and cell apoptosis. In in vivo burn-wound treatment, this MICH promptly integrates with injured surrounding tissue to provide hydration microenvironment and physicochemical ECM for burn wounds. Importantly, the MICH matrix suppresses tissue ROS production, reducing the inflammatory response, prompting re-epithelization and neoangiogenesis during wound healing. Meanwhile, the remodeling skin treated with MICH matrix demonstrates low collagen deposition and normal dermal collagen architecture. Overall, the MICH prevents burn wound progression and enhances skin regeneration, which might be a promising biomaterial for burn-wound care and other disease therapy induced by oxidative stress.

Yang CS, Luo P, Zeng Z, Wang H, Malafa M, Suh N

Mol Carcinog. 2020 Apr;59(4):365-389. doi: 10.1002/mc.23160. Epub 2020 Feb 3.

Abstract

α-Tocopherol (α-T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α-T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α-T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α-T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ- and δ-forms of tocopherols and tocotrienols (T3). In comparison with α-T, these forms have much lower systemic bioavailability but have shown stronger cancer-preventive activities in many studies in animal models and cell lines. γ-T3 and δ-T3 generally have even higher activities than γ-T and δ-T. In this article, we review recent results from human and laboratory studies on the cancer-preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.

Li X, Jarosz AC, El-Sohemy A, Badawi A

Nutr Health. 2020 Mar 31:260106020912945. doi: 10.1177/0260106020912945. [Epub ahead of print]

Abstract

BACKGROUND:

Genetic and nutritional factors play an important role in inflammatory response and diseases. CXCL10 is a critical biomarker that is involved in multiple inflammatory diseases, and elevated levels of CXCL10 have been associated with the development of several chronic and infectious diseases. In contrast, micronutrients can attenuate inflammatory responses. Single nucleotide polymorphisms in the pro-inflammatory cytokine genes such as IL-1β at rs16944 contributed to a number of inflammatory disorders and may substantiate the convergance between chronic and infectious diseases.

AIM:

This study aims to identify the modifying effect of nutritional factors on the association between IL-1β genotypes and CXCL10 levels.

METHODS:

Participants (N = 386) were healthy males and females from the Toronto Nutrigenomics and Health study recruited from the University of Toronto. Levels of micronutrients and inflammatory markers were measured in plasma. IL-1β genotypes were extracted from the Affymetrix 6.0 SNP chip.

RESULTS:

CXCL10 levels were not different across different IL-1β genotypes. Among those with the GA genotype, elevated CXCL10 levels were observed with higher than median ascorbic acid (β = 0.004 ± 0.002, P = 0.047) or higher than median vitamin D status (β = 0.003 ± 0.002, P = 0.044). Among participants with the AA genotype, subjects with low α-tocopherol status had elevated levels of CXCL10 (β = -0.016 ± 0.007, P = 0.012).

CONCLUSION:

The association between IL-1β rs16944 genotype and CXCL10 levels was modified by the levels of ascorbic acid, α-tocopherol and vitamin D. These findings may aid in understanding the combined effect of genetic and dietary factors in the development of various infectious and chronic diseases in which IL-1β and CXCL10 may play an etiological role.

Shvachko LP, Zavelevich MP, Gluzman DF, Telegeev GD

Exp Oncol. 2020 Mar;42(1):31-34.

Abstract

Placental-like alkaline phosphatase (PLAP) is expressed by many tumors and can be detected in sera of patients with various cancers. Its aberrant expression has been considered to be potentially useful as tumor marker. However, the biological background of the role of this aberrant alkaline phosphatase (AP) in cancer is still unclear. The expression of various forms of AP in cells of chronic myeloid leukemia (CML) has not yet been studied.

AIM:

To analyze the expression patterns of various AP forms in cells originated from CML patients in blast crisis and to modify their expression by vitamin E.

MATERIALS AND METHODS:

RNA extracted from leukemic cells was converted to cDNA and real-time reverse transcription polymerase chain reaction was performed using SYBR Green protocol with primers to tissue non-specific alkaline phosphatase (TNAP), intestinal alkaline phosphatase and CCAAT-enhancer-binding proteins alpha (C/EBPα). To analyze the modulation of expression of APs and C/EBPα, CML cells were incubated with 100 µM vitamin E.

RESULTS:

We have observed the aberrant expression of mRNA intestinal alkaline phosphatase in CML cells that upon sequencing demonstrated the significant alignment with PLAP sequence while no gene homology with tissue placental alkaline phosphatase (PAP) was revealed. Vitamin E decreases mRNA PLAP expression and increases mRNA TNAP expression. Moreover, along with down-regulation of aberrant PLAP and up-regulation of TNAP, vitamin E increases C/EBPα mRNA expression.

CONCLUSION:

The loss of TNAP in CML may contribute to pathogenesis of this disease. PLAP may be considered as a putative target in differentiation therapies in myeloid neoplasms. Our findings suggest the potential role of vitamin E as the inducer of differentiation potential of leukemic cells in CML.

Sakamoto T, Maebayashi K, Tsunoda Y, Imai H

J Clin Biochem Nutr. 2020 Mar;66(2):116-123. doi: 10.3164/jcbn.19-51. Epub 2020 Jan 31.

Abstract

Glutathione peroxidase 4 (GPx4) is a unique antioxidant enzyme that directly reduces the phospholipid hydroperoxides (PLOOH) generated in biomembranes using glutathione as the reductant. We have previously reported that the Caenorhabditis elegans gpx-quad mutant, which lacks all homologous genes of GPx4 has a reduced lifespan compared with the wild-type. However, the mechanisms underlying the lifespan reduction remain unclear. By monitoring the change in PLOOH production with age, we found that PLOOH was elevated in the gpx-quad mutants compared with the wild-type during the reproductive period. Administration of vitamin E not only reduced the PLOOH content but also prolonged the lifespan of the gpx-quad mutants. In contrast, vitamin C did not extend the lifespan of the gpx-quad mutants. Interestingly, we found that the inhibition of lipid peroxidation by vitamin E during 5 to 10 days after hatching is important to extend the lifespan of C. elegans. These results suggest that production of PLOOH during the reproductive period strongly influences the lifespan of C. elegans.

Yan G, Chen R, Xiong N, Song J, Wang X, Tang R

Colloids Surf B Biointerfaces. 2020 Mar 28;191:111000. doi: 10.1016/j.colsurfb.2020.111000. [Epub ahead of print]

Abstract

To promote the targeted cancer therapy, the pH-sensitive small molecule nanodrug self-assembled from amphiphilic vitamin B6-E analogue conjugate was successfully constructed. Herein, water-soluble vitamin B6 with pKa (5.6) was chemically conjugated to lipid-soluble vitamin E succinate (α-TOS), which showed selective cancer cell killing ability and this amphiphilic small molecule vitamin conjugate could self-assemble to be free nanoparticles (NPs) and doxorubicin-loaded NPs (α-TOS-B6-NPs-DOX). The small molecule nanodrugs could perform the following characteristic: (i) stability in the sodium dodecyl sulfonate (SDS) solution and long-term storage stability in PBS via surface negative charge; (ii) tumor accumulation by enhanced penetration and retention (EPR) effect; (iii) improved cellular internalization by means of vitamin B6 transporting membrane carrier (VTC); and (iv) facilitating endosomal escape and rapid drug release for synergistic toxicity to tumor cells via charge reversal and ester hydrolysis at intracellular pH and/or esterase. Moreover, α-TOS-B6-NPs-DOX exhibited long blood circulation stability and significant tumor accumulation and inhibition with the decreased side effects in vivo. Thus, the pH-sensitive small molecule nanodrug self-assembled from amphiphilic vitamin B6-E analogue conjugate could be the potential drug carriers in targeted synergistic cancer therapy.

Abouelghar GE, El-Bermawy ZA, Salman HMS

Environ Sci Pollut Res Int. 2020 Mar;27(8):7886-7900. doi: 10.1007/s11356-019-06579-9. Epub 2019 Dec 30.

Abstract

Fipronil (FIP) is a highly effective, broad-use insecticide that belongs to the phenylpyrazole chemical group. It is extensively used in the agriculture and veterinary medicine for controlling a wide variety of pests. Though FIP showed lower toxicity in vertebrates than in insects, it was recognized to have a variety of toxic effects in mammals. The present study was undertaken to evaluate FIP-induced alterations in the blood biochemical markers and oxidative stress parameters in male albino mice via oral sub-acute toxicity exposure. The possible ameliorative effect of the pretreatment with selenium plus α-tocopherol (vitamin E) against the harmful effects of FIP was also investigated. Mice in FIP-test groups were exposed to different sublethal doses, i.e., 1.43, 2.87, and 4.78 mg active ingredient (AI)/kg body weight (b.w.), equal to 1/100, 1/50, and 1/30 LD₅₀ of FIP, respectively, for 28 days. Mice in the amelioration groups were orally administered with selenium + vitamin E (0.3 mg + 22.5 mg/kg b.w., respectively) 14 days prior to exposure to the higher dose (4.78 mg/kg) of FIP for another 14 days. Fipronil exposure at medium and high doses showed lowered values of red blood cell count (RBC), hematocrit (HCT), hemoglobin (HGB), white blood cell (WBC), and platelet (PLT) counts after 28-day exposure, compared to the control. All three doses caused significant increases in levels of liver-function biomarkers, i.e., aspartate amino transaminase (AST), alanine amino transaminase (ALT), alkaline phosphatase (ALP), cholesterol, and bilirubin levels compared to the control. Levels of biomarkers related to kidney functions, i.e., urea, uric acid, and creatinine, increased significantly than these of the control. Likewise, the oxidative stress indices, i.e., hydrogen peroxide (H₂O₂) and malondialdehyde (MDA), significantly increased at the higher and medium doses, while antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD), decreased significantly. On the other hand, prior administration of selenium + vitamin E in the FIP-exposed mice led to restore values of most hematological parameters nearly to these of the control. Also, the levels of AST, total protein, and creatinine seemed to be restored to the control values. Interestingly, pretreatment with selenium + vitamin E restored the levels of antioxidant enzymes, CAT and SOD, to the control values, whereas, oxidative stress indices, H₂O₂ and MDA, remained significantly high. It is our thought that the sublethal dose less than 1.43 mg/kg b.w. of commercial formulation of FIP (COACH^® 200 SC) could be considered as no-observed-adverse-effect-level(NOAEL) under our present experimental conditions at short-term toxicity study. On the other hand, the higher sublethal doses, 4.78 and 2.87 mg/kg b.w., induced significant adverse effects in biomarkers and may be deleterious to human health following long-term exposure.

Jafarian Asl P, Niazmand R, Yahyavi F

Heliyon. 2020 Mar 25;6(3):e03592. doi: 10.1016/j.heliyon.2020.e03592. eCollection 2020 Mar.

Abstract

In the present study, modified extraction methods using supercritical CO₂ were investigated in order to obtain high-added value compounds from rapeseed oil deodorizer distillate and comparisons were done with modified Soxhlet extraction (solvent extraction + silica). For supercritical fluid extraction (SFE), the optimal extraction parameters were temperature of 40 °C, pressure of 350 bar (for phytosterols), 400 bar (for tocopherol), 5 wt% ethanol as co-solvent, and saponification pretreatment. The optimized SFE procedure led to the recovery of three main phytosterols (50 wt % β-sitosterol, 23.91 wt % Brassicasterol, and 36.25 wt % Campesterol) and only α-tocopherol. Moreover, there was no synergistic effect with saponification pretreatment + co-solvent and the efficiency and concentration of target compounds were less than supercritical CO₂ + co-solvent. Also, comparative Data showed that the efficiency of phytosterols and tocopherols was approximately three times higher (p < 0.05) in SFE relative to modified Soxhlet extraction. Furthermore, the use of ethanol (5 wt %) as co-solvent, improved phytosterols and tocopherol efficiency and purity. The SFE technique offers various advantages over the modified Soxhlet extraction technique, including increasing the solubility of tocopherols and sterols by using CO₂+ co-solvent, minimized usage of toxic organic solvents and increased purity of extracted products.