Evaluation of UVA-mediated oxidative damage to proteins and lipids in extracorporeal photoimmunotherapy

The combination of UVA and 8-methoxypsoralen (8-MOP) is known for the abili ty to produce reactive oxygen species (ROS) that react subsequently with DN A, lipids and proteins. In most studies concerned with UVA effects mediated by free radicals, UVA doses higher than those exhibiting beneficial clinic al results in extracorporeal photoimmunotherapy (ECPI) were used. The prese nt study was undertaken to determine markers of oxidative stress in plasma and cells from the buffy coat using conditions relevant for ECPI (cumulativ e UVA dose at the sample level less than or equal to 2 J/cm(2)). Plasma exp osed to UVA of 20 J/cm(2) resulted in protein oxidation as well in crosslin king and fragmentation revealed by electrophoresis, Exposure of the buffy c oat and plasma to considerably lower doses of UVA (up to 2 J/cm(2)) combine d with various 8-MOP concentrations resulted neither in an increase of malo ndialdehyde as a marker of lipid peroxidation nor in a changed electrophore tic protein pattern. In these same experiments the total antioxidative capa city decreased to 65% of the initial value, suggesting that the antioxidati ve defense of plasma is able to cope with oxidative stress under ECPI condi tions. These results were confirmed by data from 10 patients with scleroder ma or cutaneous T-cell lymphoma during ECPI treatment. The present results suggest that, although ROS are formed during ECPI, gross oxidative damage d oes not occur. It is, however, possible, that specific effects mediated by oxygen radicals may co-trigger the photoimmunomodulatory effects of ECPI.