Hautschutzmoleküle – Quo vadis? Von der Chemoprävention bis zur kulturell geprägten Dermatoästhetik

Zusammenfassung

Basierend auf dem sich akkumulierenden Wissen zu genetischen, molekularen und zellulären Funktionen der Haut, hat sich die Suche nach neuen Hautschutzmolekülen intensiviert, die 1.) präventiv sind hinsichtlich extrinsischen Noxen, die für eine vorzeitige Hautalterung verantwortlich sind, die 2.) präventiv oder kurativ gegen schwere, chronifizierende Hauterkrankungen wirken und 3.) präventiv hinsichtlich einer Tumorigenese eingesetzt werden können. Zugleich sollen solche Stoffe auch pflegende Eigenschaften im Sinne einer Dermatoästhetik aufweisen. Das Konzept einer personalisierten Medizin lässt sich dabei beispielhaft an dem Organ Haut verwirklichen, da genetische und epigenetische Daten hinreichend zuverlässig erhoben werden und in Therapieoptionen einfließen können. Ein therapeutisches Beispiel für Hautschutz und -pflege ist die topische Anwendung von Komponenten des Glutathion-Detoxifikationssystems, das reduzierte Glutathion (GSH).

Abstract

The increasing knowledge about the genetic, molecular and cellular function of the skin has worldwide intensified the search for novel molecules which can protect the skin against cumulative external noxious compounds, against skin diseases and tumorigenesis. Concerning the human skin, the challenges of a personalized medicine, which is the management of health and the treatment of diseases, which is specific for the genetic and epigenetic make-up of an individual skin, can be met and concomitantly serve a model. The topic application of a novel compound, which is part of the natural and highly conserved cellular glutathione detoxification system, the reduced glutathione (GSH) might become a therapeutic strategy for radioprotection and tumorigenesis either by functioning as scavanger of oxidative stress or by enhancing detoxification of chemical carcinogens and noxious environmental chemicals in combination with general skin care.

• Literatur

• 1 Bernard JJ, Gallo R. Protecting the boundary: The sentinel role of host defense peptides in the skin. Cell Mol Life Sci 2011; 68: 189-199
• 2 Zänker KS, Mihich E, Liu E. Personalized Cancer Medicine 2011. Toward Individualized Cancer Treatments. XV. International Fritz Bender Symposium Held on February 21 to 23, 2011 at Matrix, Biopolis, Singapore. Transl Oncol 2011; 4: 198-201
• 3 Kowalczyk MC, Spears E, Narog M et al. Modulation of biomarkers related to tumor initiation and promotion in mouse skin by a natural ß-glucoronidase inhibitor and its precursor. Oncol Rep 2011; 26: 551-556
• 4 Cibin TR, Devi DG, Abraham A. Chemoprevention of Two-Stage Skin Cancer in vivo by Saraca asoca. Integr Cancer Ther 19.07.2011; (Epub ahead of print)
• 5 Shu YY, Maibach HI. Estrogen and Skin. Therapeutic Options. Am J Clin Dermatol 29.06.2011; (Epub ahead of print)
• 6 Liu X, Nugoli M, Laferriere J et al. Stromal retinoic acid receptor promotes mammanry gland tumorigenesis. Proc Natl Acad Sci USA 2011; 108: 774-779
• 7 Elias PM, Crumrine D, Paller A. Pathogenesis of the cutaneous phenotype in inherited disorders of cholesterol metabolism: Therapeutic implications for topical treatment of these disorders. Dermatoendocrinol 2011; 3: 100-106
• 8 Shimizu I, Cruz A, Chang KH et al. Treatment of Squamous Cell Carcinoma in Situ: A Review. Dermatol Surg 18.07.2011; (Epub ahead of print)
• 9 Smith V, Walton S. Treatment of facial basal cell carcinoma. A review. J Skin Cancer 27.04.2011; (Epub ahead of print)
• 10 Kalivar SK, Mantena SK, Meeran SM. Silymarin protects epidermal keratinocytes from ultraviolet radiation-induced apoptosis and DNA damage by a nucleotide excision repair mechanism. PLoS 2011; 6 (6): e21410
• 11 Zänker KS. Immunology of Invertebrates: Humoral. In: Encyclopedia of Life Sciences (ELS). Chicester: John Wiley & Sons; 2010. DOI: 101002 (9780470015902.a0000.pub2)
• 12 Asakura M, Miura H. Imiquimod 5% cream for the treatment of nasal lesion of metastatic renal cell carcinoma. Dermatol Ther 2011; 24: 375-377
• 13 Fishelevich R, Zhao Y, Tuchina P et al. Imiquimod-Induced TLR7 Signaling Enhances Repair of DNA Damage Induced by Ultraviolet Light in Bone Marrow-Derived Cells. J Immunol 15.07.2011; (Epub ahead of print)
• 14 Bourquin C, Hotz C, Noerenberg D et al. Systemic cancer therapy with a small molecule agonist of Toll-like receptor 7 can be improved by circumventing TLR tolerance. Cancer Res 15.07.2011; (Epub ahead of print)
• 15 Gallwitz B. Incretin-Based Therapies for the Treatment of Type 2 Diabetes – DPP-4 Inhibitors and Incretin Mimetics. In: Masur K, Thevenod F, Zänker KS, eds. Diabetes and Cancer. Epidemiological Evidence and Molecular Links. Front Diabetes. 19. Basel: Karger; 2008: 30-43
• 16 Masur K, Schwartz F, Entschladen F et al. DPPIV inhibitors extend GLP-2 mediated tumor promotings effects in intestinal cancer cells. Regul Peptides 2007; 137: 147-155
• 17 Marchetti C, Di Carlo A, Facchiano E et al. High mobility group box 1 is a novel substrate for dipeptidase IV. Diabetologica 08.06.2011; (Epub ahead of print)
• 18 Gunasekaren K, Muthukumaravel S, Sahu SS et al. Glutathione S transferase activity in Indian vectors of malaria: A defense mechanism against DDT. J Med Entomol 2011; 48: 561-569
• 19 Abel EL, Bubel JD, Simper MS. Protection against 2-chloroethyl ethyl sulfide (CEES) – induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway. Toxicol Appl Pharmacol 23.06.2011; (Epub ahead of print)
• 20 Paromov V, Kumari S, Brannon M et al. Protective effect of liposome-encapsulated glutathione in a human epidermal model exposed to a mustard gas analog. J Toxicol 30.05.2011; (Epub ahead of print)
• 21 Georgii JL, Amadeu TP, Seabra AB et al. Topical S-nitrosoglutathione-releasing hydrogel improves healing of rat ischaemic wounds. Tissue Eng Regen Med 2011; 5: 612-619
• 22 Fekecs T, Kadar Z, Battyani Z et al. Changes in oxidative stress in patients screened for skin cancer after solid-organ transplantation. Transplant Proc 2010; 42: 2336-2338
• 23 Slocum SL, Kensler TW. Nrf2: control of sensitivity to carcinogens. Archiv Toxicol 2011; 85: 273-284
• 24 Wu KC, Cui JY, Klaassen CD. Beneficial Role of Nrf2 in Regulating NADPH Generation and Consumption. Toxicol Sci 20.07.2011; (Epub ahead of print)
• 25 Ladizinski B, Mistry N, Kundu RV. Widespread use of toxic skin lightening compounds: medical and psychosocial aspects. Dermatol Clin 2011; 29: 111-123
• 26 Rajaratnam R, Halpern J, Salim A et al. Interventions for melasma. Cochrane Datebase Syst Rev 07.07.2010; ((7)) CD003583
• 27 Roulin A, Almasi B, Meichtry-Stier KS et al. Eumelanin- and pheomelanin-based colour advertise resistance to oxidative stress in opposite ways. J Evol Biol 11.07.2011; (Epub ahead of print)
• 28 Arjinpathana N, Asawanonda P. Glutathione as an oral whitening agent: A randomized, double-blind, placebo-controlled study. J Dermatolog Treat 05.06.2010; (Epub ahead of print)
• 29 Manceau M, Domingues VS, Mallorino R. The developmental role of Agouti in color pattern evolution. Science 2011; 330: 1062-1065
• 30 Jablonski NG, Chaplin G. Colloquium paper: human skin pigmentation as an adaptation to UV radiation. Proc Natl Acad Sci USA 2010; 107 (Suppl 2): 8962-8968