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FOTOPROTEÇÃO ORAL Prof. Leandro Medeiros Farmacêutico e doutorando em Inovação Terapêutica | UFPE Coordenador da pós-graduação em fitoterapia na prática multidisciplinar | IDE Cursos Coordenador do núcleo de pós-graduação em farmácia | IDE Cursos Membro do Grupo de Trabalho em Fitoterapia | CRN6 Secretário-geral | CRF-PE Fotoproteção oral @prof_leandromedeiros CONTEXTUALIZAÇÃO Fotoproteção oral @prof_leandromedeiros Considerações iniciais sobre os fotoprotetores orais • Suplementos nutricionais que possuem o objetivo reduzir a agressão provocada pela exposição da pele à radiação UV • Não são capazes de impedir a inflamação, mas são úteis na redução da intensidade do fotodano, fotocarcinogênese e fotoenvelhecimento • Atuam potencializando a resposta antioxidante, colaborando com o sistema antioxidante exógeno Gonzalez et al., 2015 Fotoproteção oral @prof_leandromedeiros Do que são compostos os fotoprotetores orais? Vitamina A Vitamina C Vitamina E Ácidos graxos essenciais Nicotinamida Selênio, Zinco, Manganês Compostos bioativos isolados de plantas Carotenóides Polifenóis Terpenóides Organossulfurados Taninos Alcalóides Compostos bioativos isolados de animais Carnosina Coenzima Q10 Nutrientes Gonzalez et al., 2015 Mukthar et al. 2009 pub Talor and Blair, 2009 Fotoproteção oral @prof_leandromedeiros cytochrome P450 family, cyclooxygenases, and lipoxygenases. All possible sources of ROS, the whole anti-oxidative system of the skin as well as all cellular damages are summarized in Figure 1. Mecanismos de agressão oxidativa cutânea Richter et al., 2015 Figure 1. Schematic of the interplay between different ROS sources and the anti-oxidative @prof_leandromedeiros Fotoproteção oral systems in the skin. All ROS sources discussed in this manuscript are exemplified in black NUTRIENTES E COMPOSTOS BIOATIVOS COM USO POTENCIAL EM FOTOPROTEÇÃO Análise das evidências Fotoproteção oral @prof_leandromedeiros Tomato soup Vegetable juice Watermelon Canned, condensed Processed Red, fresh 9.77 17.47 11.48 3.99 7.28c 4.10a 245 g 240 mL (∼250 g) 280 g a USDA 1998. USDA-NCI Carotenoid Database for U.S. Foods. Nutrient Data Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville Human Nutrition Research Center, Riverdale, Maryland. b Source: From Ref. 10. c Source: From Ref. 12. d Source: From Ref. 13. Carotenóides With very few exceptions, lycopene from natural plant sources exists in the all-trans form, which is the most thermodynamically stable configuration (20–22). As a polyene, lycopene readily undergoes cis–trans isomerization. As a result of the (11) conjugated carbon–carbon double bonds in its backbone, lycopene can be theoretically arranged in 1056 different geometric configurations (Fig. 2). Although a large number of geometric isomers are possible for lycopene, Pauling (23) and Zechmeister • (20) have found that only certain ethylenic groups of a lycopene molecule can participate in cis–trans isomerization reactions because of steric hindrance. Interconversion of isomers is thought to take place with exposure to thermoenergy, absorption of light, or by involvement in specific chemical reactions. Cis isomers of lycopene have chemical and physical characteristics distinctly different from those of their all-trans counterpart. Some of these differences include lower melting point, decreased color Grupo de mais de 700 moléculas presentes em espécies vegetais, com função de fotossíntese OH HO α-carotene zeaxanthin Carotenos HO β-carotene β-cryptoxanthin OH HO all-trans lycopene lutein Figure 1 Fotoproteção oral Oxicarotenos Representative structures of common carotenoids. @prof_leandromedeiros Betacaroteno Doses de 25 mg/dia de betacaroteno isolado, ou como uma mistura de carotenóides, durante 12 semanas, reduz o eritema cutâneo pós-exposição UV, em indivíduos sensíveis ao sol. A presença da Vitamina E (500 UI) no grupo 2 não gerou diferença significativa na redução do fotoeritema. Houve redução significativa da contagem de células de Langerhans em ambos os grupos em ambos os estudos Stahl et al., 2000 Stahl et al., 2003 Fotoproteção oral @prof_leandromedeiros Betacaroteno 286 Wolfgang Köpcke and Jean Krutmann Estimates with 95% confidence intervals (CI) • • Doses de até 180 mg/dia, podem aumentar a proteção contra queimaduras solares Efeitos observados com, no mínimo, 10 semanas de suplementação Favors Control Study name Favors Carotene SMD 95% CI 06-Garmyn -0.112 [-1.171,0.948] 07-Gollnick 0.597 [-0.485,1.678] 09-Heinrich 1.339 [0.453,2.224] 10-Lee 2.303 [1.225,3.38] 11-Mathews 0.397 [-0.349,1.143] 12-McArdle 0.00 [-0.98,0.98] 15-Stahl 1.191 [0.128,2.254] 0.802 [0.201,1.403] (z = 2.6159 , p = 0.0089 ) Pooled (random effects) -2 0 1 2 -1 Standardized Mean Difference (SMD) 3 4 Std diff in means Figure 1. Forest plot for meta-analysis of b-carotene supplementation vs placebo on sunburn protection. Fotoproteção oral 3 10 2 1 9 15 7 (Table 4). Under these conditions, the fixed and t model effects showed very similar and significant contrast to the first meta-analysis, however, the d supplementation was no longer a significant mode able (P = 0.1064). Köpcke and Krutmann , 2008 DISCUSSION This meta-analysis indicates that b-carotene suppl of humans is effective in providing protection a @prof_leandromedeiros Betacaroteno 116 Johnson and Russell β-Carotene 15′ 14′ 12′ 10′ 8′ 8′CHO 10′CHO 8′COOH 10′COOH 12′CHO 12′COOH 14′COOH CHO Retinal COOH CH2OH Retinol Retinoic Acid Figure 1 !-Carotene conversion to vitamin A (retinal, retinol, and retinoic acid). Central cleavage by carotene monooxygenase or CMOI between bonds 15 and 15′ forms retinal directly. A second cleavage enzyme (CMOII) cleaves !-carotene excentrically at the 9′ –10′ position. Cleavage at other bonds forms apocarotenals (CHO). Apocarotenals may be oxidized to apocarotenoic acids (–COOH), which could form retinoic acid. Apocarotenals may be oxidized to apocarotenoic acids (–COOH), which could form retinoic acid. Johnson & Russel, 2010 Fotoproteção oral Compared with carrots (a source of !-carotene), @prof_leandromedeiros !-carotene is given in the absence of fat, no detectable Betacaroteno Ensaios pré-clínicos mostram ação pró-oxidante potencial em fibroblastos (aumento de heme oxigenase [HO-1]) Efeitos fotoprotetores do betacaroteno podem não ocorrer em todos os indivíduos Ar ch ives of Bioch em ist r y a n d Bioph ysics Vol. 389, No. 1, Ma y 1, pp. 1– 6, 2001 doi:10.1006/a bbi.2001.2313, a va ila ble on lin e a t h t t p://www.idea libr a r y.com on MINIREVIEW UV Light, Beta-carotene and Human Skin—Beneficial and Potentially Harmful Effects H a n s K. Biesa lski 1 a n d Ut e C. Ober m u eller -J evic Departm en t of B iological Ch em istry an d N u trition , Un iversity of H oh en h eim , Fru w irth strasse 12, 70593 S tu ttgart, Germ an y Received Sept em ber 7, 2000; pu blish ed on lin e Apr il 6, 2001 Fotoproteção oral h ypot h esized in t h e 1950s (4). La t er , be fou n d t o pr even t en dogen ou s (ch lor op n ou s ph ot osen sit iza t ion in ba ct er ia , a pla n t s (5). Mor eover , bet a -ca r ot en e t r ea t ed wit h h em a t opor ph yr in (6) a n d in g fr om ph ot osen sit ivit y t o visible lig or a l a dm in ist r a t ion of bet a -ca r ot en e h fu l t ool for t h er a py in pa t ien t s wit h er Basu-Modak t opor ph yrand ia (E P PTyrrell,1993 ) 2 (8). Th is h a s lea d t t h a t bet a -ca r ot en e m igh t a1999 lso h a ve pr Jones, t ies in n or m a l skin a n d t h u s pr even t Over exposu r e t o su n ligh t pr ovokes r ea ct ion wh ich clin ica lly m a n ifest s it s Ch r on ic exposu r e t o su n lea ds t o pr em (“ph ot oa gin g”) a n d in cr ea ses t h e r isk o S o la r ra d ia tio n is o n e o f th e m o s t im p o rta n t e n v iro n m e n ta l s tre s s a g e n ts fo r h u m a n s k in , c a u s in g s u n bu rn , p re m a tu re s k in a g in g , a n d s k in c a n c e r. B e ta -c a ro te n e is d is c u s s e d to p ro te c t a g a in s t p h o to o x id a tiv e s tre s s a n d th u s p re v e n t s k in d a m a g e . Th o u g h be ta -c a ro te n e h a s be e n s u c c e s s fu lly u s e d a g a in s t p h o to s e n s itiv ity in p a tie n ts w ith e ry th ro p o ie tic p ro to p o rp h y ria , its be n e fi c ia l p o te n tia l in n o rm a l s k in is s till u n c e rta in . A n u m be r o f e x p e rim e n ta l s tu d ie s in d ic a te p ro te c tiv e e ffe c ts o f be ta -c a ro te n e a g a in s t a c u te a n d c h ro n ic m a n ife s ta tio n s o f s k in p h o to d a m a g e . Ho w e v e r, m o s t c lin ic a l s tu d ie s h a v e fa ile d to c o n v in c in g ly d e m o n s tra te its be n e fi c ia l e ffe c ts s o fa r. N e v e rth e le s s , in ta k e o f o ra l be ta -c a ro te n e s u p p le m e n ts be fo re s u n e x p o - @prof_leandromedeiros Betacaroteno Ar ch ives of Bioch em ist r y a n d Bioph ysics Vol. 389, No. 1, Ma y 1, pp. 1– 6, 2001 doi:10.1006/a bbi.2001.2313, a va ila ble on lin e a t h t t p://www.idea libr a r y.com on Parece não reduzir ocorrência de quetarose solar ou câncer de pele associado à exposição solar MINIREVIEW UV Light, Beta-carotene and Human Skin—Beneficial and Potentially Harmful Effects H a n s K. Biesa lski 1 a n d Ut e C. Ober m u eller -J evic Departm en t of B iological Ch em istry an d N u trition , Un iversity of H oh en h eim , Fru w irth strasse 12, 70593 S tu ttgart, Germ an y Received Sept em ber 7, 2000; pu blish ed on lin e Apr il 6, 2001 Fotoproteção oral S o la r ra d ia tio n is o n e o f th e m o s t im p o rta n t e n v iro n m e n ta l s tre s s a g e n ts fo r h u m a n s k in , c a u s in g s u n bu rn , p re m a tu re s k in a g in g , a n d s k in c a n c e r. B e ta -c a ro te n e is d is c u s s e d to p ro te c t a g a in s t p h o to o x id a tiv e s tre s s a n d th u s p re v e n t s k in d a m a g e . Th o u g h be ta -c a ro te n e h a s be e n s u c c e s s fu lly u s e d a g a in s t p h o to s e n s itiv ity in p a tie n ts w ith e ry th ro p o ie tic p ro to p o rp h y ria , its be n e fi c ia l p o te n tia l in n o rm a l s k in is s till u n c e rta in . A n u m be r o f e x p e rim e n ta l s tu d ie s in d ic a te p ro te c tiv e e ffe c ts o f be ta -c a ro te n e a g a in s t a c u te a n d c h ro n ic m a n ife s ta tio n s o f s k in p h o to d a m a g e . Ho w e v e r, m o s t c lin ic a l s tu d ie s h a v e fa ile d to c o n v in c in g ly d e m o n s tra te its be n e fi c ia l e ffe c ts s o fa r. N e v e rth e le s s , in ta k e o f o ra l be ta -c a ro te n e s u p p le m e n ts be fo re s u n e x p o - h ypot h esized in t h e 1950s (4). La t er , be fou n d t o pr even t en dogen ou s (ch lor op n ou s ph ot osen sit iza t ion in ba ct er ia , a pla n t s (5). Mor eover , bet a -ca r ot en e tDarlington r ea t ed wit h h emet a t opor yr in (6) a n d al.,ph 2003 in g fr om ph ot osen sit ivit y t o visible lig Green et ofal., or a l a dm in ist r a t ion bet a1999 -ca r ot en e h fu l t ool for t h er a py in pa t ien t s wit h er Frieling, 2000 2 t opor ph yr ia (E P P ) (8). Th is h a s lea d t t h a t bet a -caBiesalski, r ot en e m igh t a2001 lso h a ve pr t ies in n or m a l skin a n d t h u s pr even t Over exposu r e t o su n ligh t pr ovokes r ea ct ion wh ich clin ica lly m a n ifest s it s Ch r on ic exposu r e t o su n lea ds t o pr em (“ph ot oa gin g”) a n d in cr ea ses t h e r isk o @prof_leandromedeiros Betacaroteno Não existe UL estabelecida para o betacaroteno Suplementação de 20 mg/dia foi associado positivamente sobre o aumento da incidência de câncer de pulmão e próstata em fumantes Lepalla, 2000 Bjelakovic, 2007 Fotoproteção oral @prof_leandromedeiros microfibrillar network and dietary supplementation gives partial protection. Representative photomicrographs of fibrillin-1 staining of presupplemented skin at baseline (unirradiated) (a) and 24 h post-UVR (b) showing a truncated fibrillin-rich microfibrillar network following UVR (arrows indicate the presence of microfibrils). This remodelling was offset by dietary supplementation with both olive oil [unirradiated (c), irradiated (d)] and tomato paste with olive oil [unirradiated (e), irradiated (f)]. Scale bar, 50 lm. Licopeno Postsupplementation, olive oil Postsupplementation, tomato paste Consumo de 55 g de molho de tomate (equivalente a 16 mg de licopeno) Redução das concentração deradiation MMP-1 Fig 5. Acute ultraviolet (UVR) induces matrix metalloproteinase (MMP)-1 (p = 0,04) expression and this is abrogated by dietary supplementation with tomato paste. Representative photomicrographs of MMP-1 staining of presupplemented skin at baseline (unirradiated) (a) and 24 h post-UVR (b) showing an induction of this enzyme. This induction was partially offset by dietary supplementation with tomato paste [unirradiated (c), irradiated (d)]. The arrows highlight positively stained cells. Scale bar, 50 lm. Unirradiated Manteve as concentrações de objective erythemal measurements fibrilina-1 (a) (b) (c) (d) Postsupplementation, tomato paste compared with the visual assessment of the MED. An MED is derived using an interval scale of UVR change, meaning that small alterations in erythemal sensitivity may go undetected, while erythema measurements provide a more sensitive tool in assessing the impact of potentially protective agents. The degree of protection observed would not provide clinically useful protection against sunburn erythema, but indicates some abrogation of UVRinduced effects on skin. Fotoproteção oral Irradiated Presupplementation Aumentou a deposição de procolágeno tipo I (p = 0,05) Reduziu concentrações de reação de cadeia de polimerase (p = 0,01) (f) (e) through transcription factor AP-1, which in turn is activated through UVR-induction of MAP kinase signalling pathways.34 We have demonstrated that a single UVR dose increased MMP1 expression in the dermis before supplementation, consistent with previous studies.30 Following tomato paste supplementaRizwan et al., 2011 tion there was inhibition of UVR-induced MMP-1 expression in the dermis, whereas the control (olive oil alone) did not effect change. This inhibitory effect of tomato paste on UVR induction of MMP-1 was@prof_leandromedeiros accompanied by a small increase in Licopeno Doses de 8 a 16 mg/dia, na forma de suplemento ou como produtos derivados do tomate, por 12 semanas, podem gerar proteção contra queimaduras solares. Human Nutrition a Research Com Supplementation with !-Carotene or a Similar Amount of Mixed Carotenoids Protects Humans from UV-Induced Erythema (Manuscript received 27 August 2002. Initial review completed 13 September 2002. Revision accepted 10 October 2002.) Ulrike Heinrich, Christine Gärtner,* Mathilde Wiebusch, Olaf Eichler,†1 Helmut Sies,†1 Hagen Tronnier and Wilhelm Stahl†2 Institut für Experimentelle Dermatologie, Universität WittenHerdecke, D-58455 Witten, Germany, *Cognis Deutschland GmbH & Co. KG, Nutrition and Health, D-40551 Düsseldorf, Germany and †Institut für Physiologische Chemie I and BiologischStahl et al.,2001 Medizinisches Forschungszentrum, Heinrich-Heine-Universität Düsseldorf, D-40001 Düsseldorf, Germany Stahl et al.,2003 Aust et al., 2005 Fotoproteção oral ABSTRACT Carotenoids are useful oral sun protectants, and supplementation with high doses of !-carotene protects against UV-induced erythema formation. We com@prof_leandromedeiros pared the erythema-protective effect of !-carotene (24 Licopeno Uso do licopeno parece ser seguro em doses de até 120 mg/ dia, por até 1 ano Maioria dos trabalhos avaliando seu potencial terapêutico em hiperplasias de próstata (benignas ou malignas) ADULT UROLOGY PHASE I-II PROSPECTIVE DOSE-ESCALATING TRIAL OF LYCOPENE IN PATIENTS WITH BIOCHEMICAL RELAPSE OF PROSTATE CANCER AFTER DEFINITIVE LOCAL THERAPY PETER E. CLARK, M. CRAIG HALL, LESTER S. BORDEN, JR, ANTONIUS A. MILLER, JENNIFER J. HU, W. ROBERT LEE, DIANA STINDT, RALPH D’AGOSTINO, JR, JAMES LOVATO, MICHELLE HARMON, AND FRANK M. TORTI ABSTRACT Objectives. To report a prospective trial of lycopene supplementation in biochemically relapsed prostate cancer. Methods. A total of 36 men with biochemically relapsed prostate cancer were enrolled in a dose-escalating, Phase I-II trial of lycopene supplementation. Six consecutive cohorts of 6 patients each received daily supplementation with 15, 30, 45, 60, 90, and 120 mg/day for 1 year. The serum levels of prostate-specific antigen (PSA) and plasma levels of lycopene were measured at baseline and every 3 months. The primary endpoints were PSA response (defined as a 50% decrease in serum PSA from baseline), pharmacokinetics, and the toxicity/tolerability of this regimen. Results. A total of 36 patients were enrolled. The median age was 74 years (range 56 to 83), with a median serum PSA at entry of 4.4 ng/mL (range 0.8 to 24.9). No serum PSA responses were observed, and 37% of patients had PSA progression. The median time to progression was not reached. Toxicity was mild, with 1 patient discontinuing therapy because of diarrhea. Significant elevations of plasma lycopene were noted at 3 months and then appeared to plateau for all six dose levels. The plasma levels for doses between 15 and 90 mg/day were similar, with additional elevation only at 120 mg/day. Conclusions. Lycopene supplementation in men with biochemically relapsed prostate cancer is safe and well tolerated. The plasma levels of lycopene were similar for a wide dose range (15 to 90 mg/day) and plateaued by 3 months. Lycopene supplementation at the doses used in this study did not result in any discernible Clark et al.,2006 Fotoproteção oral @prof_leandromedeiros Camellia sinensis Planta rica em polifenóis da família das catequinas No Brasil, há grande variabilidade padronizações de extratos à base de Camellia sinensis Fotoproteção oral OH OR2 OH OH OH O HO OH B O HO A R2 C OH OR1 OH Epicatechin: R1=R2=H Epigallocatechin: R1=H; R2=OH Epicatechin-3-gallate: R1=Galloyl: R2=H Epigallocatechin-3-gallate: R1=Galloyl: R2=OH O O HO OR1 OH Theaflavin: R3=R2=H Theaflavin 3-gallate: R1=Galloyl; R2=H Theaflavin: 3′-gallate: R1=H: R2=Galloyl Theaflavin: 3,3′-digallate: R1=R2=Galloyl Fig body fat (45% clearly establish the efficacy of tea@prof_leandromedeiros in the prevention of crease), and i cardiovascular disease. Camellia sinensis As catequinas podem reduzir a lesão ao DNA induzida por UVA/UVB Modelos em animais indicam que o extrato reduz a lesão oxidativa cutânea, inflamação cutânea e hiperplasia epidermal associada à radiação UV Elmets et al.,2001 Katiyar, Ahmad, Mukhtar, 2000 Fotoproteção oral @prof_leandromedeiros statistically significant difference between active and placebo (P = 0.62; Figure 4). Similarly, no statistically significant difference between treatment groups was found after multiple imputation or per-protocol analyses. Camellia sinensis GREEN TEA CATECHINS A 1.350 mg, 3x/dia, do extrato de Camellia sinensis (equivalente a 1.080 mg/dia de catequinas) não foi superior ao placebo quanto à redução de eicosanóides (ácido hidroxieicosatetraenóico / PGE2) de neutrófilos e células T CD3+. • t = 12 semanas (n = 50) Downloaded from ajcn.nutrition.org by guest on April 10, 2016 • FIGURE 5 UVR-induced PGE2 and 12-HETE production at basel and after 12 wk of supplementation. Mean 1 SEM concentration of FIGURE 4 UVR-induced neutrophil and T-cell infiltration at baseline PGE2 and (B) 12-HETE in suction blister fluid from UVR-exposed and after 12 wk of supplementation. Representative immunohistochemistry unexposed skin at baseline and post-supp (n = 20 active; n = 21 placeb of (A) neutrophils and (B) CD3+ T cells in ultraviolet-exposed * P , 0.05, **and P ,unex0.01, and *** P , 0.001 compared with unirradia skin (Wilcoxon’s Rank test). MED, minimal erythema dose; PG posed skin at baseline and post-supp. Mean + SEM number of (C) Signed neutroE2; post-supp, = 22 active; n = 25 after supplementation; UVR, ultraviolet rad phils and (D) CD3+ T cells per high-power field (nprostaglandin tion; 12-HETE, 12-hydroxyeicosatetraenoic acid. Farrar et al., 2015 Fotoproteção oral placebo). **P , 0.01 and ***P , 0.001, compared with unirradiated skin (Wilcoxon’s Signed Rank test). hpf, high-power field; MED, minimal erythema dose; post-supp, after supplementation; UVR, ultraviolet radiation. 16.3 pg/mL; P = 0.35; Figure 5A). Similarly, there was no s nificant difference in concentration of 12-HETE in UVR-expos @prof_leandromedeiros Camellia sinensis • Há evidências de benefícios em seres humanos com o uso tópico de catequinas de C. sinensis, em exposição UVA/UVB Elmets et al., 2001 Katiyar et al., 1999 Fotoproteção oral @prof_leandromedeiros Pinus pinaster (Pycnogenol®) • Produto padronizado em 65 a 75% de procianidinas totais Fotoproteção oral @prof_leandromedeiros Pinus pinaster (Pycnogenol®) Pode reduzir a hiperpigmentação cutânea Promoveu aumento da DEM na dose de 1,1 mg/kg, 2x/ dia (4 semanas), com posterior aumento para 1,66 mg/kg, 2x/dia (4 semanas) Efeito mediado pela redução da expressão de NF-kB Fotoproteção oral Review Skin Pharmacol Physiol 2016;29:13–17 DOI: 10.1159/000441039 Received: July 9, 2015 Accepted after revisio Published online: Octo French Maritime Pine Bark Extract (Pycnogenol®) Effects on Human Skin: Clinical and Molecular Evidence Susanne Grether-Beck Alessandra Marini Thomas Jaenicke Jean Krutmann IUF, Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany Key Words Pycnogenol® Ni et al., 2001 can affect human (for a2001 recent monogra Saliou etskinal., · Pine bark extract · Pigmentation · Skin barrier Krutmann and Humbert [1]). Initially, m studies have focused on the2016 capacity of suc Grether-Beck et al., Abstract Nutritional strategies to benefit skin health are of growing importance. Current approaches mainly involve nutritional supplements containing antioxidants which were initially designed to protect human skin against ultraviolet radia- provide protection against harmful effects (UV) radiation on human skin. From thes now generally accepted that oral photoprote ciple works, although the time kinetics to ac able photoprotection as well as the magnit protection that can be achieved markedl @prof_leandromedeiros Polypodium leucotomus Extrato padronizado em ácidos orgânicos totais (0,66%), expressos em ácido caféico e ácido ferúlico Estes compostos geram controle do eritema fotoinduzido, mecanismos inflamatórios e suas respostas celulares (angiogênese, fotocarcinogênese e elastose solar) Fotoproteção oral was a provem crease related flamm munoh the im to pre As a compe would skin. I UV li of PL Fig. 1 Polypodium leucotomos. The benefits of an aquatic fern originating in Central America have been used for centuries by Native given Americans as an anti-inflammatory agent, which today has applicaangiog tion, with its natural protective mechanisms against the impact of reduct ultraviolet light [3]. Photograph: Copyright Ferndale Laboratories, elasto MI, USA; used with permission Middelkamp-Hup MA., 2004 provem Bathia, 2015pressi example, ingenol mebutate gel comes from the Australian peroxi plant Euphorbia peplus [1], sinecatechins ointment is a metall derivative of the Chinese tea leaves derived from Camellia atinoc sinensis [2], and these therapies and aloe vera, among @prof_leandromedeiros p53 g many others, have been available to dermatologists for clooxy antioxidant, immunoregulatory, anti-inflammatory, and antitumorigenic effects in the context of sunburn, photodermatoses, chronic skin damage, photoaging, and skin cancer were included (n = 18 of 55). Table 1 cross-references PL photoprotective effects along with the cellular or molecular mechanisms involved and the relevant experimental study. uting to UV-induced immunosuppression.3 Antioxidant properties Studies have demonstrated that irradiation causes activation of endogenous antioxidant systems and increased glutathione (GSH) consumption to form oxidized glutathione (GSSG). PL has been shown to inhibit glutathione oxidation in blood and epidermis by allosterically modulating enzymes such as catalase.10,11 In rats treated with PL, oxidized glutathione (GSSH) levels were decreased in both non-irradiated and irradiated groups. GSSH levels in irradiated animals were fourfold lower than in rats that Polypodium leucotomus Results Overview of the effects of ultraviolet radiation on the skin Systemic UV irradiation can result in acute injuries (i.e., erythema, swelling, pain) and long-term damage (i.e., Table 1 Polypodium leucotomos photoprotective effects along with the cellular or molecular mechanisms involved. Note that some mechanisms are interconnected Protective mechanism Cellular/molecular level References Anti-inflammatory Reduction of UV-induced macrophage and neutrophil infiltration Inhibition of UV-induced Cox-2 expression Blocks TNF-a, iNOS, AP-1, NF-jB p53 activation Removal of UV-induced photoproducts and prevents formation of cyclobutan pyrimidine dimers Enhances natural antioxidant system Preservation of Langerhans cells and function Blocks t-UCA photoisomerization and photodecomposition Preserves cell viability and inhibits cytoskeletal disarray Inhibits matrix metalloproteinases 2, 5, 12 5 9 5, 11 2, 5, 11 4, 10–13 2, 5, 10, 12, 13 10, 16, 17 1 6 Decrease DNA mutagenesis Immunoregulation Cell cycle and cellular integrity Cox, cyclooxygenase; iNOS, inducible nitric oxide synthase; t-UCA, trans-urocanic acid; TNF, tumor necrosis factor; UV, ultraviolet. International Journal of Dermatology 2014 ª 2014 The International Society of Dermatology El-Haj and Goldenstein, 2014 Fotoproteção oral @prof_leandromedeiros Outros produtos com evidências preliminares na fotoproteção oral • Punica granatum (romã) • Lycium barbarum (goji) • Micronutrientes (vitamina E, vitamina C) Natural Medicines Database, 2016 Fotoproteção oral @prof_leandromedeiros CONSIDERAÇÕES FINAIS Fotoproteção oral @prof_leandromedeiros CONSIDERAÇÕES FINAIS • Não há evidências de que os suplementos antioxidantes possam substituir os fotoprotetores orais. É razoável sua utilização associada aos tópicos. • Maioria dos estudos com limitações metodológicas (controle dietético, amostra pequena) • Custos de estudos em seres humanos dificultam sua realização • Limitações da legislação sanitária quanto a alegação de uso nos rótulos de suplementos nutricionais • Observações a respeito da biodisponibilidade dos ingredientes ativos Biba, 2014 Fotoproteção oral @prof_leandromedeiros Obrigado! Instagram/Periscope: @prof_leandromedeiros Facebook: @leandro.a.medeiros E-mail: [email protected] www.idecursos.com.br Fotoproteção oral @prof_leandromedeiros