Topically Applied Vitamin C and Cysteine Derivatives Protect Against UVA-induced Photodegradation of Suprofen in Ex Vivo Pigskin¶

Abstract

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 (l‐ascorbic 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 μmol/cm2; these values were 60% for a NAC dose of 10 μmol/cm2 and 50% for a CYSET dose of 5 μmol/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.

Non‐invasive monitoring of oxidative skin stress by ultraweak photon emission measurement. II: biological validation on ultraviolet A‐stressed skin

“…Afterwards, round pieces ( d =5 cm) were punched out, packed in an airtight plastic bag, and stored at 4 °C until measurement. Porcine skin is a useful ex vivo model for human skin because it is readily available and closely resembles human skin with regard to anatomical and biochemical properties (20–22).…”

Non‐invasive monitoring of oxidative skin stress by ultraweak photon emission (UPE)‐measurement. I: mechanisms of UPE of biological materials

“…Afterwards, round pieces ( d =5 cm) were punched out, packed in an airtight plastic bag and stored at 4 °C until measurement. Porcine skin is a useful ex vivo model for human skin because it is readily available and closely resembles human skin with regard to anatomical and biochemical properties (6–8).…”