title: Degradation of hyaluronic acid by photosensitized riboflavin in vitro. Modulation of the effect by transition metals, radical quenchers, and metal chelators.
abstract: The effect of photoexcited riboflavin (RF) on the viscosity of hyaluronic acid (HA) solutions has been investigated. UV irradiation of RF causes under aerobic conditions fragmentation of HA and a decrease in the viscosity of its solutions. A decrease of HA viscosity occurs in PO(4)-buffered solutions and is accelerated by high pH, Fe2+ (but much less so by Fe3+), certain metal chelators, and horseradish peroxidase (HRP); it is partially inhibited by catalase and less so by superoxide dismutase (SOD). The reactivity of the system was completely blocked by Tris, ethanol, aspirin, d-manitol, dimethylthiourea (DMTU), dimethylsulfoxide (DMSO), and sodium azide. These results indicate that the most likely chemical species involved in the reaction is the hydroxyl radical. Singlet oxygen ((1)O(2)) generation is suggested by the ability of NaN3 and DMSO to completely inhibit the reactivity of the system. These two agents, however, may also interact with OH. radical, as well and suppress the reactivity of the system. H(2)O(2) and O(2).- seem also to be produced in significant amounts, because catalase and SOD partially block the reactivity of the system. The effect of HRP may be due to hydrogen subtraction from HA and H(2)O(2) reduction to water. Photoexcitation of RF may potentially occur in vitro and in vivo in the organs and tissues that are permeable to light, such as the eye or skin, and damage HA and other cell-matrix components causing inflammation and accelerating aging.
authors.affiliation: INSERM-U.349, Lariboisière Hospital, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Frati
authors.forename: A M
authors.initials: AM
authors.lastname: Khatib
authors.forename: P
authors.initials: P
authors.lastname: Front
authors.forename: A
authors.initials: A
authors.lastname: Panasyuk
authors.forename: F
authors.initials: F
authors.lastname: Aprile
authors.forename: D R
authors.initials: DR
authors.lastname: Mitrovic
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000737:chemistry; D008353:Mannitol / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology; D010100:Oxygen / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D012256:Riboflavin / Q000737:chemistry* / Q000528:radiation effects; D026082:Singlet Oxygen; D019810:Sodium Azide; D013482:Superoxide Dismutase / Q000378:metabolism; D013582:Synovial Fluid / Q000737:chemistry; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014466:Ultraviolet Rays; D014783:Viscosity
chemical_list: D001386:Azides; D002614:Chelating Agents; D008670:Metals; D017382:Reactive Oxygen Species; D026082:Singlet Oxygen; D017665:Hydroxyl Radical; D008353:Mannitol; C038983:1,3-dimethylthiourea; D006820:Hyaluronic Acid; D019810:Sodium Azide; D002374:Catalase; D013482:Superoxide Dismutase; D013890:Thiourea; D001241:Aspirin; D010100:Oxygen; D012256:Riboflavin; D004121:Dimethyl Sulfoxide