Proteome-wide changes in primary skin keratinocytes exposed to diesel particulate extract-A role for antioxidants in skin health

Rajagopalan P, Jain AP, Nanjappa V, Patel K, Mangalaparthi KK, Babu N, Cavusoglu N, Roy N, Soeur J, Breton L, Pandey A, Gowda H, Chatterjee A, Misra N

J Dermatol Sci. 2019 Oct 15. pii: S0923-1811(19)30273-7. doi: 10.1016/j.jdermsci.2019.08.009.

Abstract

BACKGROUND:

Skin acts as a protective barrier against direct contact with pollutants but inhalation and systemic exposure have indirect effect on keratinocytes. Exposure to diesel exhaust has been linked to increased oxidative stress.

OBJECTIVE:

To investigate global proteomic alterations in diesel particulate extract (DPE)/ its vapor exposed skin keratinocytes.

METHODS:

We employed Tandem Mass Tag (TMT)-based proteomics to study effect of DPE/ DPE vapor on primary skin keratinocytes.

RESULTS:

We observed an increased expression of oxidative stress response protein NRF2, upon chronic exposure of primary keratinocytes to DPE/ its vapor which includes volatile components such as polycyclic aromatic hydrocarbons (PAHs). Mass spectrometry-based quantitative proteomics led to identification 4490 proteins of which 201 and 374 proteins were significantly dysregulated (≥1.5 fold, p ≤ 0.05) in each condition, respectively. Proteins involved in cellular processes such as cornification (cornifin A), wound healing (antileukoproteinase) and differentiation (suprabasin) were significantly downregulated in primary keratinocytes exposed to DPE/ DPE vapor. These results were corroborated in 3D skin models chronically exposed to DPE/ DPE vapor. Bioinformatics analyses indicate that DPE and its vapor affect distinct molecular processes in skin keratinocytes. Components of mitochondrial oxidative phosphorylation machinery were seen to be exclusively overexpressed upon chronic DPE vapor exposure. In addition, treatment with an antioxidant like vitamin E partially restores expression of proteins altered upon exposure to DPE/ DPE vapor.

CONCLUSIONS:

Our study highlights distinct adverse effects of chronic exposure to DPE/ DPE vapor on skin keratinocytes and the potential role of vitamin E in alleviating adverse effects of environmental pollution.

Zahid S, Khalid H, Ikram F, Iqbal H, Samie M, Shahzadi L, Shah AT, Yar M, Chaudhry AA, Awan SJ, Khan AF, Rehman IU

Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:438-447. doi: 10.1016/j.msec.2019.03.080. Epub 2019 Mar 23.

Abstract

With an increase in the demand for skin regeneration products, there is a noticeable increase in developing materials that encourage, wound healing and skin regeneration. It has been reported that antioxidants play an important role in anti-inflammatory reactions, cellular proliferation and remodeling phase of wound healing. While consideration all these factors, a novel α-tocopherol acetate (vitamin E) (VE) loaded bi-layered electrospun membrane, based on lower polycaprolactone (PCL) layer and upper polylactic acid (PLA) layer, was fabricated through electrospinning. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), in-vitro degradation studies, swelling studies and VE release studies were performed to evaluate structural, physical and in-vitro behavior of membranes. Biological properties of membranes were evaluated through cell proliferation assay, cell adhesion studies, live/dead cell assay and CAM assay. SEM images showed that the average diameter of nanofibers ranged from 1 to 6 μm, while addition of VE changed the diameter and morphology of fibers. Bi-layered membranes showed significant swelling behavior through water uptake, membranes loaded with 30% VE showed 8.7% and 6.8% degradation in lysozyme and H₂O₂ respectively. 20% and 30% VE loaded membranes followed Korsmeyer-Peppas and first order drug release kinetics followed by non-fickian drug release kinetics. Membranes showed non-toxic behavior and supported cell proliferation via alamar blue assay, cell adhesion via SEM, cell viability via live/dead assay and wound healing by scratch assay. CAM assay showed that membranes having VE supported angiogenesis and showed significant formation of blood vessels making it suitable for skin regeneration and wound healing. Results showed that large surface area of nanofibers, porous structure and biocompatible nature are suitable for targeted clinical applications.

Nasef SM, Khozemy EE, Kamoun EA, El-Gendi H

Int J Biol Macromol. 2019 Jul 5;137:878-885. doi: 10.1016/j.ijbiomac.2019.07.033. [Epub ahead of print]

Abstract

Crosslinked hydrogel composite membranes based on polyvinyl alcohol (PVA) and chitosan-loaded AgNO₃ and vitamin E were prepared using gamma irradiation. Chitosan has been used as antimicrobial blend materials to provide further biocompatibility for the prepared composite hydrogel membranes. The crosslinking reaction between PVA and chitosan owing to gamma irradiation was verified and characterized by FTIR analysis, while the morphology of hydrogel composite membranes was investigated by SEM. Important parameters affecting on hydrogel membranes formation, such as copolymer concentration, irradiation dose, AgNO₃ concentration, plasticizer, and vitamin E of PVA/chitosan membranes were evaluated and discussed in details. In addition, the mechanical and thermal properties of hydrogel composite membranes were examined to evaluate the possibility of its application for wound dressings. The results revealed that the gelation (%) of hydrogel membranes increased dramatically with PVA composition, irradiation dose and glycerol content up to 20%; however, it decreased with AgNP incorporation due to the viscosity of copolymer composition is hyper-increased. The swelling ratio of composed hydrogel membranes decreased notably with increasing the radiation dose and incorporation of AgNP, due to reducing of the crosslinking degree of formed hydrogel membranes. PVA-Cs-Ag composed hydrogel membranes showed significant antimicrobial activity in particular against Streptococcus mutans due to the presence of AgNP in membranes, compared to other bacteria and fungi microbes. Thus, the PVA/chitosan/AgNO₃-Vit.E hydrogel composite membranes showed satisfactory properties for use as wound dressing materials.

Vaz S, Silva R, Amaral MH, Martins E, Sousa Lobo JM, Silva AC

Colloids Surf B Biointerfaces. 2019 Jul 1;179:242-249. doi: 10.1016/j.colsurfb.2019.03.036. Epub 2019 Apr 3.

Abstract

Lipid-based nanosystems, such as nanostructured lipid carriers (NLC) and nanoemulsions (NE) have been described as promising alternatives to conventional formulations for increase skin hydration. Besides, these systems have been used as efficient vehicles for lipophilic molecules that improve skin properties (e.g. vitamin E). In this study, we performed comparative investigations between hydrogels formulations containing vitamin E-loaded NLC (HG-NLC_VE) and vitamin E-loaded nanoemulsion (HG-NE_VE). The experiments started with particle size measurements, which showed no significant differences between nanoparticles/nanodroplets sizes after incorporation in the hydrogel net (386 nm vs. 397 nm for HG-NLC_VE and 402 nm vs. 514 nm for HG-NE_VE). Afterwards, in vitro biocompatibility studies in human keratinocytes were carried out, being observed that the lipid-based nanosystems were more cytotoxic for the cells before incorporation in the hydrogel. Finally, the formulations hydration potential and sensory attributes for skin application were evaluated by in vitro occlusion tests and in vivo human experiments. The results showed that the HG-NLC_VE exhibited the best occlusive properties, whereas the HG-NE_VEperformed a faster skin hydration effect. Furthermore, the latter was selected as the most attractive for skin application, although the HG-NLC_VE was described as more suitable to obtain a long-lasting effect. This study demonstrated the in vitro and in vivo safety and hydration potential of hydrogels containing vitamin E-loaded lipid-based nanosystems. These results establish a basis to assess the cutaneous use of these systems, despite more in vivo experiments, for longer periods and in more volunteers, are required before commercialization.

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).

Hajizadeh K, Alizadeh Charandabi SM, Hasanzade R, Mirghafourvand M

Complement Ther Med. 2019 Jun;44:1-8. doi: 10.1016/j.ctim.2019.03.014. Epub 2019 Mar 22.

Abstract

OBJECTIVES:

A systematic review was conducted to assess the effect of vitamin E on the severity and duration of Cyclic Mastalgia compared to vitamin B6, fish oil, herbal medicines and placebo.

DESIGN:

A systematic review and meta-analysis of clinical trials.

METHODS:

A search was carried out in PubMed, Cochrane Library, Embase, Scopus and Google Scholar and Persian databases for articles published from 1980 to 2018. The data obtained were analyzed in RevMan and reported in forest plots. The Odds Ratio (OR) was used to find the effect for the dichotomous data and the Standardized Mean Difference (SMD) for the continuous data. The heterogeneity of the studies was assessed using I² and the Random Effects Model was used instead of the Fixed Effects Model if I²>25%.

RESULTS:

A total of 1051 titles and abstracts were extracted. Fourteen articles ultimately remained, and 11 of them were entered into the meta-analysis. The meta-analysis showed significant differences between vitamin E and placebo in the severity (SMD=-0.51; 95% CI=-0.21 to -0.82) and duration (MD=-1.47; 95% CI=-0.91 to -2.57) of cyclic mastalgia, although herbal medicines had a greater effect on the severity of mastalgia than vitamin E (SMD = 0.51, 95% CI = 0.06 to 0.96).

CONCLUSION:

Although herbal medicines are more effective than vitamin E, vitamin E reduces both the severity and duration of the disorder compared to placebos, which only reduce its severity, and can therefore be considered a treatment with minimum side-effects. Due to the high heterogeneity of the studies, the researchers recommend further research on the subject using a standard tool based on the CONSORT statement.

Gou S, Del Rio-Sancho S, Singhal M, Laubach HJ, Kalia YN

Eur J Pharm Sci. 2019 May 10;135:22-31. doi: 10.1016/j.ejps.2019.05.007. [Epub ahead of print]

Abstract

Radiation induced fibrosis is a common side-effect after radiotherapy. Pentoxifylline is reported to reverse radiation injuries when used in conjunction with D-α-tocopherol. However, pentoxifylline has a short half-life, limited oral bioavailability, and induces several systemic adverse effects. The objective of this study was to investigate the feasibility of using Er:YAG fractional laser ablation to enable simultaneous cutaneous delivery of pentoxifylline and D- α –tocopherol succinate from poly(lactide-co-glycolide) microparticles prepared using the freeze-fracture technique. In vitro release experiments demonstrated the different release profiles of the two molecules, which were influenced by their very different lipophilicities and aqueous solubilities. Experiments were then performed to investigate the effect of laser fluence on pore depth and so determine the pore volume available to host the topically applied microparticles. Application of the pentoxifylline and D-α-tocopherol succinate containing microparticles, prepared with RESOMER® RG 502H, to laser porated skin for 48 h, resulted in simultaneous delivery of pentoxifylline (69.63 ± 6.41 μg/cm²; delivery efficiency 46.4%) and D-α-tocopherol succinate (33.25 ± 8.91 μg/cm²; delivery efficiency 22.2%). After deposition into the micropores, the poly(lactide-co-glycolide) microparticles containing pentoxifylline and D-α-tocopherol succinate could serve as an intraepidermal depot to enable sustained drug delivery after micropore closure and thereby reduce the need for repeated microporation.

Russo T, Currò M, Ferlazzo N, Caccamo D, Perrone P, Arena S, Antonelli E, Antonuccio P, Ientile R, Romeo C, Impellizzeri P

Urol Int. 2019 Apr 16:1-7. doi: 10.1159/000499846. [Epub ahead of print]

Abstract

BACKGROUND:

Lichen sclerosus (LS) is a disease of the skin of unclear etiology that can occur in the foreskin. Topical therapy with corticosteroids is recommended, but they can have side effects.

OBJECTIVES:

We aimed to compare the effects of ozonides with vitamin E acetate (OZOILE) versus topical corticosteroid in children undergoing circumcision.

METHOD:

Twenty children undergoing circumcision were treated before surgery: 10 children with OZOILE cream and 10 with 0.1% mometasone furoate once a day for 7 days. Ten age-matched patients with LS of the foreskin without any treatment were recruited as controls. Transcript levels of proinflammatory and anti-inflammatory cytokines and e-cadherin were evaluated in removed foreskins by qRT-PCR.

RESULTS:

OZOILE and steroid topical treatment produced a similar reduction of TNF-α and IL-1β mRNA levels in foreskins from patients with LS when compared to untreated patients (p < 0.001). OZOILE and steroid treatment caused an increase in the transcript levels of IL-13 and e-cadherin in the foreskin of patients affected by LS in comparison to untreated foreskin (p < 0.001).

CONCLUSIONS:

On the basis of our biochemical data, a randomized clinical trial might be useful to verify the actual clinical effect of OZOILE as alternative treatment to corticosteroids in children affected by LS of the foreskin.

Singh I, Nair RS, Gan S, Cheong V, Morris A

Pharm Dev Technol. 2018 Oct 3:1-7. doi: 10.1080/10837450.2018.1509347. [Epub ahead of print]

Abstract

The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol-rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright ‘Franz-type’ diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log p values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6 µg/cm² h and 23.0 µg/cm² h respectively, compared to the control with a flux of 16.2 µg/cm² h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil.

Fiume MM, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks JG Jr, Shank RC, Slaga TJ, Snyder PW, Andersen FA, Heldreth B

Send to Int J Toxicol. 2018 Sep/Oct;37(2_suppl):61S-94S. doi: 10.1177/1091581818794455.

Abstract

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 14 tocopherols and tocotrienols and concluded these ingredients are safe as used in cosmetics. The tocopherols are reported to function in cosmetics as antioxidants or skin-conditioning agents; in contrast, tocotrienols are not reported to function as an antioxidants in cosmetics but as a light stabilizer, oral care agent, or skin-conditioning agent. The Panel reviewed the new and existing animal and clinical data to determine the safety of these ingredients and found it appropriate to extrapolate the existing information to conclude on the safety of all the tocopherols and tocotrienols.