Evidence that certain phototoxic drugs photosensitize urocanic acid isomerization

Trans to cis photoisomerization of epidermal urocanic acid (UCA) has been proposed as a primary event in UV-induced immunosuppression. 8-Methoxypsoralen (8-MOP) in combination with WA radiation (PUVA) is used for photochemotherapy of several immunoiogically based skin disorders, and PUVA is known to cause immunosuppression. We examined the photointeraction of 8-MOP and other skin photosensitizing drugs (amiodarone, ciprofloxacin, doxycycline and ketoprofen) with trans-UCA in vitro. In oxic conditions 8-MOP did not enhance the ability of radiation from standard PUVA fluorescent sources (0.2% radiation below 320 nm) to produce cis-UCA, When oxygen was removed, some 8-MOP photosensitization could be detected. 8-MOP, ciprofloxacin and ketoprofen also enhanced inefficient UCA photoisomerization by radiation from a filtered tungsten halogen source (0.02% radiation below 320 nm). 8-MOP photosensitization is essential for radiation from PUVA tubes to have a therapeutic or immunosuppressive effect. We have shown in vitro that 8-MOP does not enhance cis-UCA production by this source. Extrapolation of our data to the in vivo situation suggests that UCA may not be involved in either the therapeutic or the immunosuppressive effect of PUVA.