Photosensitizing properties of 6-methoxy-2-naphthylacetic acid, the major metabolite of the phototoxic non-steroidal anti-inflammatory and analgesic drug nabumetone.
The photobiological properties of 6-methoxy-2-naphthylacetic acid (6-MNAA) were studied using a variety of in vitro phototoxicity assays: photohemolysis, photoperoxidation of linoleic acid, photosensitized degradation of histidine and thymine and the Candida phototoxicity test. 6-MNAA was phototoxic in vitro. 6-MNAA reduced nitro blue tetrazolium (NBT) when irradiated with lambda > or = 300 nm in deoxygenated aqueous buffer solution (pH 7.4). NBT can be reduced by reaction with the excited state of 6-MNAA subject to interference with molecular oxygen. The photohemolysis rate was inhibited by the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO), sodium azide (NaN3) and reduced glutathione (GSH). Photoperoxidation of linoleic acid and photosensitized degradation of histidine and thymine were significantly inhibited by sodium azide and reduced glutathione. 6-MNAA was phototoxic to C. albicans, C. lipolytica and C. tropicalis. A mechanism involving singlet oxygen, radicals, and electron transfer reactions is suggested for the observed phototoxicity.
Canudas
N
N
Laboratorio de Fotoquímica y Fotobiología, Departamento de Química, Universidad Simón Bolívar, Venezuela. ncanudas@usb.ve
Zamora
D
D
Villamizar
J E
JE
Fuentes
J
J
Castelli
C
C
Taddei
A
A
D000332:Aerobiosis; D000693:Anaerobiosis; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002074:Butanones / Q000493:pharmacokinetics*; D002175:Candida / Q000187:drug effects / Q000254:growth & development / Q000528:radiation effects; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D017484:Dermatitis, Phototoxic; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006639:Histidine / Q000737:chemistry / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D008027:Light; D019787:Linoleic Acid / Q000737:chemistry / Q000528:radiation effects; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D000077430:Nabumetone; D009280:Naphthaleneacetic Acids / Q000494:pharmacology*; D009580:Nitroblue Tetrazolium / Q000737:chemistry / Q000528:radiation effects; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000494:pharmacology*; D013941:Thymine / Q000737:chemistry / Q000528:radiation effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D009280:Naphthaleneacetic Acids; D017319:Photosensitizing Agents; D009580:Nitroblue Tetrazolium; D006639:Histidine; D004247:DNA; C044612:6-methoxy-2-naphthylacetic acid; D019787:Linoleic Acid; D000077430:Nabumetone; D013941:Thymine