Molecular mechanism of drug photosensitization. Part 3. Photohemolysis sensitized by diflunisal.
The lysis of red blood cells photosensitized by diflunisal (DFN) was investigated. Photohemolysis is inhibited by butylated hydroxyanisole and reduced glutathione, but is unaffected by mannitol and enhanced by sodium azide; the presence of oxygen markedly reduces the lysis which is accelerated in anaerobic conditions. These results contrast with those expected for a photodynamic mechanism. High lytic activity is observed for pre-irradiated solutions, mainly under anaerobic conditions. Direct irradiation of DFN in buffer solution at pH 7.4 leads to the formation, under anaerobic conditions, of compound 2'-(2''',4'''-difluoro-3''-carboxy-[1'',1'''-biphenyl]-4''-oxy)-4'- fluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylic acid (PhP), whereas under aerobic conditions formation of PhP is accompanied by unidentified photo-oxidation products; only compound PhP displays strong lytic activity. The overall results for DFN-photosensitized hemolysis suggest a mechanism involving a concerted action of free radicals, superoxide anion, singlet oxygen and sensitizer photoproducts.
De Guidi
G
G
Dipartimento di Scienze Chimiche, Università di Catania, Italy.
Chillemi
R
R
Giuffrida
S
S
Condorelli
G
G
Cambria Famá
M
M
D000332:Aerobiosis; D000693:Anaerobiosis; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D004061:Diflunisal / Q000494:pharmacology* / Q000528:radiation effects; D006461:Hemolysis / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008027:Light; D016877:Oxidants / Q000494:pharmacology; D010782:Photolysis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016877:Oxidants; D011838:Radiation-Sensitizing Agents; D004061:Diflunisal