Pyrrolidine dithiocarbamate inhibits UVB-induced skin inflammation and oxidative stress in hairless mice and exhibits antioxidant activity in vitro

Ultraviolet B (UVB) irradiation may cause oxidative stress- and inflammation-dependent skin cancer and premature aging. Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and inhibits nuclear factor-kappa B (NF-kappa B) activation. In the present study, the mechanisms of PDTC were investigated in cell free oxidant/antioxidant assays, in vivo UVB irradiation in hairless mice and UVB-induced NR kappa B activation in keratinocytes. PDTC presented the ability to scavenge 2,2'-azinobis-(3-ethyl benzothiazoline-6-sulfonic acid) radical (ABTS), 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) and hydroxyl radical ((OH)-O-center dot); and also efficiently inhibited iron-dependent and -independent lipid peroxidation as well as chelated iron. in vivo, PDTC treatment significantly decreased UVB-induced skin edema, myeloperoxidase (MPO) activity, production of the proinflammatory cytokine interleukin-1 beta (IL-1 beta), matrix metalloproteinase-9 (MMP-9), increase of reduced glutathione (GSH) levels and antioxidant capacity of the skin tested by the ferric reducing antioxidant power (FRAP) and ABTS assays. PDTC also reduced UVB-induced ha degradation in keratinocytes. These results demonstrate that PDTC presents antioxidant and anti-inflammatory effects in vitro, which line up well with the PDTC inhibition of UVB irradiation-induced skin inflammation and oxidative stress in mice. These data suggest that treatment with PDTC may be a promising approach to reduce UVB irradiation-induced skin damages and merits further pre-clinical and clinical studies. (C) 2014 Elsevier B.V. All rights reserved.