Ultraviolet radiation and reactive oxygen generation as inducers of keratinocyte apoptosis: Protective role of tea polyphenols

Ultraviolet A ( UVA) radiation produces serious damage to skin, especially to dermis, but its damage to epidermis and responsible mechanisms are not f ully understood. Studies were thus undertaken to investigate the effects of UVA or reactive oxygen species (ROS) on lipid peroxidation, cell cycle, an d apoptosis in primary cultured rat keratinocytes and to determine the poss ible protect ive effects of tea polyphenols (TPP). UVA or ROS increased the release of plasma enzyme lactate dehydrogenase (LDH), and increased lipid peroxidation production (malondialdehyde, MDA), but decreased the activity of glutathione peroxidase (GSH-Px), indicating that UVA or ROS were cytosta tic and peroxidizing to keratinocytes. TPP stabilized and protected cell me mbranes from ROS or UVA by inhibiting the release of LDH, lowering MDA leve ls, and increasing GSH-Px activity. Flow cytometry ( FCM) analysis revealed that UVA or ROS decreased the proliferative index (PI); hence the cell gro wth was blocked in the S/G2 phase, with an increase in the percentage of ap optosis in primary keratinocytes. TPP modified the UVA or ROS-induced chang es in PI and apoptosis. TPP may be useful to protect keratinocytes from UVA irradiation. In summary, these data demonstrated that UVA damage to skin k eratinocytes in vitro was similar to that for ROS and that TPP protects aga inst UVA-induced cytotoxicity by inhibiting lipid peroxidation and apoptosi s.