Molecular mechanism of drug photosensitization. 5. Photohemolysis sensitized by Suprofen.
Red blood cell lysis photosensitized by Suprofen (SPF) and the photolysis of the drug were investigated. The photohemolysis process occurs at a higher rate in anaerobic than aerobic conditions. The effect of additives demonstrates the involvement of free radicals and, to a lesser extent, singlet oxygen and hydroxyl radicals in the process. Photolysis of the drug at 310-390 nm in deaerated buffered solutions (pH 7.4) leads to a decarboxylation process with the formation of p-ethylphenyl 2-thienyl ketone (I), whereas in aerated solutions formation of photoproduct I and of the photoproducts p-acetylphenyl 2-thienyl ketone (II) and p-(1-hydroxyethyl)phenyl-2-thienyl ketone (III) occurs. The photodegradation products, which were separated and characterized, show a moderate lytic and photolytic activity. The rate of SPF photodegradation decreases in the presence of oxygen and increases in the presence of hydrogen donors. The overall results lead us to propose a mechanism of SPF photodegradation and a hemolysis scheme in which cell damage is provoked principally by the direct attack of drug radicals and secondarily by singlet oxygen and hydroxyl radicals.
De Guidi
G
G
Dipartimento di Scienze Chimiche, Università di Catania, Italy.
Chillemi
R
R
Costanzo
L L
LL
Giuffrida
S
S
Sortino
S
S
Condorelli
G
G
D000332:Aerobiosis; D000693:Anaerobiosis; D001386:Azides / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects* / Q000528:radiation effects; D005978:Glutathione / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007659:Ketones / Q000032:analysis; D008353:Mannitol / Q000494:pharmacology; D010782:Photolysis; D017319:Photosensitizing Agents / Q000494:pharmacology*; D019810:Sodium Azide; D013482:Superoxide Dismutase / Q000494:pharmacology; D013496:Suprofen / Q000494:pharmacology*; D014466:Ultraviolet Rays
D001386:Azides; D007659:Ketones; D017319:Photosensitizing Agents; D002083:Butylated Hydroxyanisole; D008353:Mannitol; D019810:Sodium Azide; D013496:Suprofen; D013482:Superoxide Dismutase; D005978:Glutathione