Chemex Pharmaceuticals nordihydroguaiaretic acid (CHX 100) is a potent antioxidant also possessing antiproliferative, antitumor and lipoxygenase inhibition activities. These actions, especially its antioxidant and lipoxygenase inhibitory activities, suggest that CHX 100 may reduce the deleterious effects of acute ultraviolet light (UVL) exposure on the skin, as these effects may be associated with formation of reactive oxygen species (ROS). Such effects include erythema, edema and damage to the epidermal keratinocyte and melanocyte. In addition, the reported ability of CHX 100 to attenuate tumor development in a murine model of skin tumor initiation and promotion suggests the drug could prevent some of the deleterious effects of chronic sun exposure, eg, development of precancerous and cancerous lesions. The goal of this study is to evaluate the role of ROS in UVL-induced damage to skin cells and the ability of CHX 100 and ROS scavengers to prevent this damage.
The specific aims are to determine: 1. The effects of UVL on arachidonic acid release from, and viability of, cultured human keratinocytes and the ability of CHX 100 and ROS scavengers to alter this response. 2. The ability of CHX 100 and ROS scavengers to attenuate UVL- induced melanocyte hyperplasia and hyperpigmentation. The research is aimed at developing safe, effective topical drugs for the prevention of skin damage associated with acute and chronic sun exposure.
