Experimental studies on the mechanisms of tiaprofenic acid photosensitization.
Red blood cell lysis and histidine degradation, photosensitized by tiaprofenic acid (TIA), were investigated. Photohaemolysis was markedly enhanced in oxygenated solutions, but was also intense in the presence of nitrogen. Photohaemolysis was inhibited by butylated hydroxyanisole and reduced glutathione, but was unaffected by sodium azide, superoxide dismutase and mannitol. The TIA-induced photo-oxidation of histidine was greatly enhanced in the presence of oxygen and almost completely inhibited in solutions bubbled with nitrogen. Sodium azide, butylated hydroxyanisole and reduced glutathione inhibited the photodegradation of histidine. Phototoxicity to histidine was unaffected by mannitol and superoxide dismutase. The overall results suggest that molecular mechanisms involving free radicals and singlet oxygen are responsible for TIA-photosensitized reactions. These two in vitro models (photohaemolysis and histidine degradation) represent different mechanisms of phototoxicity, but complement one another in the investigation of potential phototoxic substances.
Figueiredo
A
A
Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal.
Ribeiro
C A
CA
Gonçalo
M
M
Baptista
A P
AP
Teixeira
F
F
D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D005978:Glutathione / Q000494:pharmacology; D006454:Hemoglobins / Q000032:analysis; D006461:Hemolysis / Q000187:drug effects* / Q000528:radiation effects; D006639:Histidine / Q000528:radiation effects*; D006801:Humans; D007700:Kinetics; D009584:Nitrogen / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D011422:Propionates / Q000494:pharmacology*; D014466:Ultraviolet Rays
D006454:Hemoglobins; D017319:Photosensitizing Agents; D011422:Propionates; C021270:tiaprofenic acid; D002083:Butylated Hydroxyanisole; D006639:Histidine; D005978:Glutathione; D009584:Nitrogen; D011188:Potassium; D010100:Oxygen