Photodegradation and in vitro phototoxicity of aceclofenac.
Aceclofenac (Airtal) (1) is a photoallergic and phototoxic anti-inflammatory and analgesic agent. This drug is photolabile under aerobic and anaerobic conditions. Irradiation of an ethanol-solution of aceclofenac under oxygen or argon at 290-320 nm affords via decarboxlation compound 2 as the main isolated and spectroscopically identified photoproduct, besides hydroxylamine derivates 3 and 4. A radical intermediate was evidenced spectrophotometrically with GSH and DTNB, as well as by the dimerization of cysteine. Red blood cell lysis photosensitized by 1-4 was investigated. Furthermore, in a lipid-photoperoxidation test with linoleic acid the in vitro phototoxicity of aceclofenac was also verified. The photoinduced generation of peroxide by compound 1 was determined during the irradiation in presence of NADPH by chemiluminescence. In relation to the photoallergic activity of this drug, the interaction of aceclofenac with human serum albumin (HSA) has been studied through fluorescence spectroscopy. No photoinduced binding was observed after irradiation of compounds 1 in the presence of human serum albumin.
Vargas
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Laboratorio de Fotoquímica, Centro de Química, Instituto Venezolano de Investigaciones Científicas I.V.I.C., Caracas, Venezuela. fvargas@ivic.ivic.ve
Rivas
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Zoltan
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Fuentes
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Padrón
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Díaz
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Izzo
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000633:toxicity*; D003545:Cysteine / Q000187:drug effects / Q000528:radiation effects; D017484:Dermatitis, Phototoxic / Q000473:pathology*; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D004912:Erythrocytes / Q000528:radiation effects; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D019787:Linoleic Acid / Q000528:radiation effects; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D049449:Luminescence; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood; D010782:Photolysis; D012709:Serum Albumin / Q000737:chemistry / Q000528:radiation effects; D014466:Ultraviolet Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016877:Oxidants; D012709:Serum Albumin; D004008:Diclofenac; D019787:Linoleic Acid; D005978:Glutathione; D003545:Cysteine; C056498:aceclofenac; D010100:Oxygen