An EPR spin trapping study of albumin protein radicals formed by the photodynamic action of haematoporphyrin.
The photodynamic action of haematoporphyrin (8,13-bis (1-hydroxyethyl)-3,7,12,17-tetramethyl-21H,23H-porphine-2,18 -dipropionic acid) has been shown to generate radical species upon isolated bovine and human serum albumins by the detection, using EPR spectroscopy, of adducts of the protein-derived radicals to spin traps. Similar radicals can also observed with fresh human serum, suggesting that similar species might be generated during in vivo photodynamic therapy. These radicals are believed to arise as a result of processes both dependent and independent of singlet oxygen formation (Type II and Type I reactions respectively). The formation of these protein radicals can be inhibited by physiologically relevant antioxidants such as glutathione and ascorbate in a dose-dependent manner; the observation of similar species with fresh serum does however suggest that these defensive processes can be easily overwhelmed. The relevance of these findings to the photodynamic therapy of tumours is discussed.
Timmins
G S
GS
Department of Chemistry, University of York, Heslington, UK.
Davies
M J
MJ
D000975:Antioxidants / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005609:Free Radicals; D005978:Glutathione / Q000494:pharmacology; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D012709:Serum Albumin / Q000187:drug effects* / Q000528:radiation effects; D012710:Serum Albumin, Bovine / Q000187:drug effects* / Q000528:radiation effects; D014508:Urea
D000975:Antioxidants; D001386:Azides; D005609:Free Radicals; D006415:Hematoporphyrins; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D014508:Urea; D005978:Glutathione