UV-induces formation of hydrogen peroxide based on the photochemistry of ketoprofen.
Ketoprofen (KP) is a potent nonsteroidal anti-inflammatory drug. However, application to the skin is problematic because the photosensitizing properties of the benzophenone moiety may cause phototoxic effects when the treated skin region is exposed to UVA light. Using capillary electrophoresis with electrochemical detection we are able to differentiate the peroxides formed during illumination of KP-containing solutions of linoleic acid. Contrary to other profens a high amount of hydrogen peroxide was found among the reaction products. For investigation of the skin damaging effect human keratinocytes were used as models. Cell viability, DNA synthesis efficiency and intracellular concentration of peroxides were determined. Viability and proliferation behavior was not altered under the influence of KP. While lower concentrations of KP (10-100 nM) led to a protection against the UVA-induced (8 J/cm2) cell proliferation damage, higher concentrations (10-100 microM) led to an amplification of the proliferation decrease. With UVB irradiation at relevant doses the effects were lower than using UVA. Furthermore, intracellular peroxide content was increased after UV irradiation and KP addition. In conclusion some efforts have to be done to avoid these side effects in the use of KP for topical or transdermal application.
Radschuweit
A
A
Institute of Pharmaceutical Chemistry, Department of Pharmacy, Martin-Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, D-06120 Halle, Germany. radschuweit@pharmazie.uni-halle.de
Rüttinger
H H
HH
Nuhn
P
P
Wohlrab
W
W
Huschka
C
C
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry / Q000528:radiation effects; D002460:Cell Line; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D007660:Ketoprofen / Q000009:adverse effects / Q000737:chemistry* / Q000528:radiation effects*; D010777:Photochemistry; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007660:Ketoprofen; D006861:Hydrogen Peroxide