title: Skin photosensitizing agents and the role of reactive oxygen species in photoaging.
abstract: In this paper, the role of reactive oxygen species in photoaging is presented. Many photosensitizing agents are known to generate reactive oxygen species (singlet oxygen (1O2), superoxide anion (O2.-) and .OH radicals). Although photoaging (dermatoheliosis) of human skin is caused by UVB and UVA radiation, the hypothesis tested here in the pathogenesis of photoaging of human skin is the free radical theory involving the generation of reactive oxygen species by UVA (320-400 nm) radiation and their damaging oxidative effects on cutaneous collagen and other model proteins. The UVA-generated reactive oxygen species cause cross-linking of proteins (e.g. collagen), oxidation of sulfydryl groups causing disulfide cross-links, oxidative inactivation of certain enzymes causing functional impairment of cells (fibroblasts, keratinocytes, melanocytes, Langerhans cells) and liberation of proteases, collagenase and elastase. The skin-damaging effects of UVA appear to result from type II, oxygen-mediated photodynamic reactions in which UVA or near-UV radiation in the presence of certain photosensitizing chromophores (e.g., riboflavin, porphyrins, nicotinamide adenine dinucleotide phosphate (NADPH), etc.) leads to the formation of reactive oxygen species (1O2, O2.-, .OH). Four specific observations are presented to illustrate the concept: (1) the production of 1O2 and O2.- by UVB, UVA and UVA plus photosensitizing agents (such as riboflavin, porphyrin and 3-carbethoxypsoralens) as a function of UV exposure dose, the sensitizer concentration and the pH of the irradiated solution; (2) the formation of protein cross-links in collagen, catalase and superoxide dismutase by 1O2 and O2.- (.OH) and the resulting denaturation of proteins and enzyme activities as a function of UVA exposure dose; (3) the protective role of selective quenchers of 1O2 and O2.- (e.g. alpha-tocopherol acetate, beta-carotene, sodium azide, ascorbic acid, etc.) against the photoinactivation of enzymes and the prevention of the protein cross-linking reaction; (4) the possible usefulness of certain antioxidants or quenchers that interact with the UVA-induced generation of reactive oxygen species in the amelioration of the process of photoaging.
authors.affiliation: Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
authors.forename: M
authors.initials: M
authors.lastname: Dalle Carbonare
authors.forename: M A
authors.initials: MA
authors.lastname: Pathak
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism*; D003094:Collagen / Q000302:isolation & purification / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005609:Free Radicals; D011564:Furocoumarins / Q000494:pharmacology; D006168:Guinea Pigs; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D010100:Oxygen / Q000378:metabolism*; D011166:Porphyrins / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012256:Riboflavin / Q000494:pharmacology; D026082:Singlet Oxygen; D015595:Skin Aging / Q000187:drug effects / Q000528:radiation effects*; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D005609:Free Radicals; D011564:Furocoumarins; D006878:Hydroxides; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D013481:Superoxides; D026082:Singlet Oxygen; D017665:Hydroxyl Radical; D003094:Collagen; C017104:3-carbethoxypsoralen; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen; D012256:Riboflavin