Topically applied vitamin C and cysteine derivatives protect against UVA-induced photodegradation of suprofen in ex vivo pigskin.
Exposure of the nonsteroidal anti-inflammatory drug suprofen (SUP) to UV-radiation results in the formation of radicals, reactive oxygen species (ROS), photodecarboxylated products and photoadducts with biomacromolecules. Using an ex vivo pigskin explant model, we investigated whether topical coapplication of the water-soluble antioxidants vitamin C (Lascorbic acid, ASC), N-acetyl-L-cysteine (NAC) or L-cysteine ethylester (CYSET) with SUP reduced ultraviolet A (UVA)-induced decomposition of SUP. UVA-induced changes in antioxidant bioavailability in the stratum corneum and epidermis were also studied. Epidermal bioavailability of SUP in sham-irradiated pigskin increased 2.2- to 4.1-fold after the lowest antioxidant doses (P < 0.05). As compared with no applied antioxidant, increasing doses of all tested antioxidants resulted in increased levels of SUP and decreased levels of photoproducts (P < 0.05). A maximal protection against SUP photodegradation of 70% was found after an ASC dose of 1 micromol/cm2; these values were 60% for a NAC dose of 10 micromol/cm2 and 50% for a CYSET dose of 5 micromol/cm2. Skin antioxidant levels increased with increasing applied dose (P < 0.05); the bioavailability of CYSET was approximately three-fold lower than that of ASC and NAC. UVA exposure resulted in 30-50% consumption of the topically applied ASC or NAC in the stratum corneum, whereas CYSET was not consumed. In conclusion, the topically applied water-soluble antioxidants ASC, NAC and CYSET protect against UVA-induced decomposition of SUP by scavenging radicals and ROS. Coapplication of these antioxidants may therefore be an effective way to reduce or prevent the phototoxic effects of SUP in vivo.
Department of Medicinal Photochemistry, Leiden/Amsterdam Center for Drug Research, University of Leiden, Leiden, The Netherlands.
Ralf M W
RM
Moison
Jolanda M
JM
Rijnkels
Elena
E
Podda
Francesca
F
Righele
Federica
F
Tomasello
Sergio
S
Caffieri
Gerard M J
GM
Beijersbergen van Henegouwen
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000528:radiation effects*; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D003545:Cysteine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D013496:Suprofen / Q000378:metabolism / Q000528:radiation effects*; D013552:Swine; D014466:Ultraviolet Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D011837:Radiation-Protective Agents; D013496:Suprofen; D003545:Cysteine; D001205:Ascorbic Acid