UV-Induces Formation of Hydrogen Peroxide Based on the Photochemistry of Ketoprofen¶

Abstract

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.

Photoreactivity of the Nonsteroidal Anti-inflammatory 2-Arylpropionic Acids with Photosensitizing Side Effects¶

“…Several reports have dealt with the photochemistry of KP, both in aqueous and organic solutions (30,38,(55)(56)(57)(58)(59). Exposure of KP in oxygenated neutral aqueous media to sunlight gives rise to the typical photodecarboxylation and BZPH photoreduction products.…”

“…In acetonitrile, the singlet oxygen quantum yield has been found to be 0.39 for KP and 0.29 for KP1, values very close to that reported for BZPH (0.34) (30). Moreover, irradiated aqueous solutions of KP contain significant amounts of hydrogen peroxide which has been identified and quantitatively determined using capillary electrophoresis coupled with electrochemical detection (58). Formation of hydrogen peroxide must take place by dismutation of O 2 •Ϫ .…”

Photoreaction of Ketoprofen with Tryptophan and Tyrosine in Phosphate Buffer Solution

“…1), felbinac, flurbiprofen and indomethacin have been applied to the anti-inflammatory analgesic plaster of second-generation compress. KP is one of the most widely used NSAIDs, while the side effect on the human skin, that is to say, photosensitization in vivo was reported (1)(2)(3)(4)(5)(6)(7)(8).…”

Amperometric and voltammetric detection for capillary electrophoresis

“…A number of compounds that have been analyzed by CEEC do not fit into the broadly defined categories above; these include ferrocene [69], aniline derivatives [70], alkaloids [65,66], oxygen or peroxides [72][73][74], purine bases [12][13][14]75], nucleosides [12][13][14], and related metabolites [14,75,76]. Several drugs have been determined by CEEC including antibiotics [32,[77][78][79], beta-blockers [80], nonsteroidal anti-inflammatory drugs (NSAIDs) [81,82], and antivirals [83], as well as illicit drugs and their metabolites [84,85].…”