Molecular mechanism of drug photosensitization. 4. Photohemolysis sensitized by carprofen.
Red blood cell lysis photosensitized by carprofen (CPF) was investigated. The photohemolysis process was observed in both aerobic and anaerobic conditions. Irradiation (310-390 nm) of buffered CPF solutions at pH 7.4 in deaerated conditions leads to a dehalogenation process via intermediate radicals with formation of the compound 2-(2-carbazolyl)propanoic acid (I) in the presence of hydrogen donors. Irradiation of I produces decarboxylation via free radicals and the formation of a stable decarboxylated compound, 2-ethylcarbazole (II). The photodegradation products I and II do not show lytic activity. The dechlorinated product I shows photosensitizing ability which was studied in the presence of the red blood cells in both aerated and deaerated solution. When carried out in the presence of additives, the observed photohemolysis suggests the involvement of free radicals and singlet oxygen in the membrane damage induced by both CPF and photoproduct I irradiation, whereas there is no evidence of any role for hydroxyl radicals. Superoxide anion is involved only in the photosensitization process induced by photoproduct I.
De Guidi
G
G
Dipartimento di Scienze Chimiche, Università di Catania, Italy.
Chillemi
R
R
Costanzo
L L
LL
Giuffrida
S
S
Condorelli
G
G
D000332:Aerobiosis; D000693:Anaerobiosis; D001386:Azides / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology* / Q000528:radiation effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000528:radiation effects; D004912:Erythrocytes / Q000187:drug effects* / Q000528:radiation effects; D005978:Glutathione / Q000494:pharmacology; D006461:Hemolysis; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008081:Liposomes; D008353:Mannitol / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D019810:Sodium Azide; D013482:Superoxide Dismutase / Q000494:pharmacology; D014466:Ultraviolet Rays
D001386:Azides; D002227:Carbazoles; D008081:Liposomes; D017319:Photosensitizing Agents; D002084:Butylated Hydroxytoluene; D008353:Mannitol; D019810:Sodium Azide; D013482:Superoxide Dismutase; C007005:carprofen; D005978:Glutathione