Systemic photoprotective agents

The concept of an effective, safe systemic photoprotectant circumvents many of the shortcomings associated with the use of topical agents as a modality preventive of actinic damage. On the other hand, difficulties resulting from systemic metabolism and toxicity complicate this approach. The problems are exemplified by the fact that some agents such as the antimalarials, psoralens, and carotenoids have been successfully employed in the treatment of specific photosensitive diseases but, aside from any potential toxicities, their ameliorative effects appear to be related to the particular pathomechanisms of the responding disease rather than general photoprotection. The complexity of systemic approaches is further demonstrated by the fact that agents possessing protective properties, e.g. butylated hydroxytoluene and carotenoids, inhibit UV carcinogenesis, while others, e.g., 8-methoxypsoralen, potentiate this process. Nevertheless, from this ostensible disorder of responses, it seems apparent that those agents holding the greatest promise for future investigation are those capable of enhancing natural defense mechanisms, i.e., melanization and antiradical activity. Thus, while none of the agents reviewed here are deemed suitable as general photoprotectants, the fact that only a modest, measured protective effect can elicit a dramatic decrease in actinic damage (particularly with respect to cancer) upholds this concept as an important goal.