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      Molecular photoprotection of human keratinocytes in vitro by the naturally occurring mycosporine‐like amino acid palythine

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          Solar ultraviolet radiation ( UVR) induces molecular and genetic changes in the skin, which result in skin cancer, photoageing and photosensitivity disorders. The use of sunscreens is advocated to prevent such photodamage; however, most formulations contain organic and inorganic UVR filters that are nonbiodegradable and can damage fragile marine ecosystems. Mycosporine‐like amino acids ( MAAs) are natural UVR‐absorbing compounds that have evolved in marine species for protection against chronic UVR exposure in shallow‐water habitats.


          To determine if palythine, a photostable model MAA, could offer protection against a range of UVR‐induced damage biomarkers that are important in skin cancer and photoageing.


          HaCaT human keratinocytes were used to assess the photoprotective potential of palythine using a number of end points including cell viability, DNA damage (nonspecific, cyclobutane pyrimidine dimers and oxidatively generated damage), gene expression changes (linked to inflammation, photoageing and oxidative stress) and oxidative stress. The antioxidant mechanism was investigated using chemical quenching and Nrf2 pathway activation assays.


          Palythine offered statistically significant protection ( P < 0·005) against all end points tested even at extremely low concentrations (0·3% w/v). Additionally, palythine was found to be a potent antioxidant, reducing oxidatively generated stress, even when added after exposure.


          Palythine is an extremely effective multifunctional photoprotective molecule in vitro that has potential to be developed as a natural and biocompatible alternative to currently approved UVR filters.


          What's already known about this topic?

          • Mycosporine‐like amino acids (MAAs) are photoprotective molecules found in marine organisms but there are few data on their ability to protect skin cells from the adverse effects of solar ultraviolet radiation (UVR).

          • The European Chemicals Agency (ECHA) is concerned about the potential adverse health and ecotoxic effects of eight of 16 commonly used sunscreen filters in Europe. The Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme has expressed similar concerns.

          What does this study add?

          • Palythine, an MAA extracted from an edible seaweed, affords photoprotection against a wide range of adverse effects in HaCaT keratinocytes exposed to solar simulating and ultraviolet A radiation. Of note is protection against two types of DNA photolesions; cyclobutane pyrimidine dimers and 8‐oxo‐7,8‐dihydroguanine.

          • Palythine is also a potent antioxidant that offers protection even when added after UVR exposure.

          What is the translational message?

          • MAAs should be considered for development as natural biocompatible sunscreens that may address the concerns of the ECHA and EEAP.

          Linked Comment:  https://doi.org/10.1111/bjd.16598.


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          Most cited references 59

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          Oxidative stress in the pathogenesis of skin disease.

          Skin is the largest body organ that serves as an important environmental interface providing a protective envelope that is crucial for homeostasis. On the other hand, the skin is a major target for toxic insult by a broad spectrum of physical (i.e. UV radiation) and chemical (xenobiotic) agents that are capable of altering its structure and function. Many environmental pollutants are either themselves oxidants or catalyze the production of reactive oxygen species (ROS) directly or indirectly. ROS are believed to activate proliferative and cell survival signaling that can alter apoptotic pathways that may be involved in the pathogenesis of a number of skin disorders including photosensitivity diseases and some types of cutaneous malignancy. ROS act largely by driving several important molecular pathways that play important roles in diverse pathologic processes including ischemia-reperfusion injury, atherosclerosis, and inflammatory responses. The skin possesses an array of defense mechanisms that interact with toxicants to obviate their deleterious effect. These include non-enzymatic and enzymatic molecules that function as potent antioxidants or oxidant-degrading systems. Unfortunately, these homeostatic defenses, although highly effective, have limited capacity and can be overwhelmed thereby leading to increased ROS in the skin that can foster the development of dermatological diseases. One approach to preventing or treating these ROS-mediated disorders is based on the administration of various antioxidants in an effort to restore homeostasis. Although many antioxidants have shown substantive efficacy in cell culture systems and in animal models of oxidant injury, unequivocal confirmation of their beneficial effects in human populations has proven elusive.
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            Oxygen-radical absorbance capacity assay for antioxidants.

             Sean Cutler,  G Cao,  H Alessio (1993)
            A relatively simple but sensitive and reliable method of quantitating the oxygen-radical absorbing capacity (ORAC) of antioxidants in serum using a few microliter is described. In this assay system, beta-phycoerythrin (beta-PE) is used as an indicator protein, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a peroxyl radical generator, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox, a water-soluble vitamin E analogue) as a control standard. Results are expressed as ORAC units, where 1 ORAC unit equals the net protection produced by 1 microM Trolox. The uniqueness of this assay is that total antioxidant capacity of a sample is estimated by taking the oxidation reaction to completion. At this point all of the nonprotein antioxidants (which include alpha-tocopherol, vitamin C, beta-carotene, uric acid, and bilirubin) and most of the albumin in the sample are oxidized by the peroxyl radical. Results are quantified by measuring the protection produced by antioxidants. This solves many problems associated with kinetics or lag-time measurements. A linear correlation of ORAC value with concentration of serum. Trolox, vitamin C, uric acid, and bovine albumin is demonstrated. The coefficient of variation within a run is found to be about 2% and from run to run about 5%. Trolox, alpha-tocopherol, vitamin C, beta-carotene, uric acid, and bilirubin completely protect beta-PE from oxidation, while bovine albumin protects beta-PE only partially. On a molar basis, the relative peroxyl radical absorbance capacity of Trolox, alpha-tocopherol acid succinate, uric acid, bilirubin, and vitamin C is 1:1:0.92:0.84:0.52. Bovine albumin per unit weight has a lower peroxyl absorbing capacity than these antioxidants.(ABSTRACT TRUNCATED AT 250 WORDS)
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              Metabolites from algae with economical impact.

              In order to survive in a highly competitive environment, freshwater or marine algae have to develop defense strategies that result in a tremendous diversity of compounds from different metabolic pathways. Recent trends in drug research from natural sources have shown that algae are promising organisms to furnish novel biochemically active compounds. The current review describes the main substances biosynthesized by algae with potential economic impact in food science, pharmaceutical industry and public health. Emphasis is given to fatty acids, steroids, carotenoids, polysaccharides, lectins, mycosporine-like amino acids, halogenated compounds, polyketides and toxins.

                Author and article information

                Br J Dermatol
                Br. J. Dermatol
                The British Journal of Dermatology
                John Wiley and Sons Inc. (Hoboken )
                25 March 2018
                June 2018
                : 178
                : 6 ( doiID: 10.1111/bjd.2018.178.issue-6 )
                : 1353-1363
                [ 1 ] St John's Institute of Dermatology Faculty of Life Sciences and Medicine King's College London London U.K.
                [ 2 ] Institute of Pharmaceutical Science Faculty of Life Sciences and Medicine King's College London London U.K.
                Author notes
                [* ] Correspondence

                Antony R. Young.

                E‐mail: antony.young@ 123456kcl.ac.uk

                © 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 5, Tables: 0, Pages: 11, Words: 7638
                Funded by: BASF SE, Ludwigshafen, Germany
                Funded by: National Institute for Health Research (NIHR)
                Translational Research
                Original Articles
                Translational Research
                Custom metadata
                June 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.3 mode:remove_FC converted:05.07.2018



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