Photosensitizing properties of 6-methoxy-2-naphthylacetic acid, the major metabolite of the phototoxic non-steroidal anti-inflammatory and analgesic drug nabumetone.

Abstract

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.

• Authors: N Canudas, D Zamora, J E Villamizar, J Fuentes, C Castelli, A Taddei
• Journal: Die Pharmazie (Pharmazie) Vol. 60 Issue 8 Pg. 604-8 (Aug 2005) ISSN: 0031-7144 [Print] Germany
• PMID: 16124404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Butanones
• Naphthaleneacetic Acids
• Photosensitizing Agents
• Nitroblue Tetrazolium
• Histidine
• DNA
• 6-methoxy-2-naphthylacetic acid
• Linoleic Acid
• Nabumetone
• Thymine

Topics

• Aerobiosis
• Anaerobiosis
• Anti-Inflammatory Agents, Non-Steroidal (pharmacokinetics)
• Butanones (pharmacokinetics)
• Candida (drug effects, growth & development, radiation effects)
• DNA (drug effects, radiation effects)
• Dermatitis, Phototoxic
• Erythrocytes (drug effects, radiation effects)
• Hemolysis (drug effects, radiation effects)
• Histidine (chemistry, radiation effects)
• Humans
• In Vitro Techniques
• Light
• Linoleic Acid (chemistry, radiation effects)
• Lipid Peroxidation (drug effects, radiation effects)
• Nabumetone
• Naphthaleneacetic Acids (pharmacology)
• Nitroblue Tetrazolium (chemistry, radiation effects)
• Photochemistry
• Photosensitizing Agents (pharmacology)
• Thymine (chemistry, radiation effects)