UV-dependent quinolone-induced human erythrocyte membrane lipid peroxidation: studies on the phototoxicity of Y-26611, a new quinolone derivative.

Abstract

Quinolone antibacterial drugs are widely used as oral therapeutic agents. However, in some patients they cause ultraviolet (UV)-dependent dermatitis. Using lipid peroxidation as an index of phototoxicity, we studied the effects of a new quinolone derivative, Y-26611 together with ofloxacin, sparofloxicin and lomefloxacin on washed human erythrocyte suspensions. Irradiation of erythrocytes with UV-A or UV-B for 60 min. in the presence of Y-26611 (30-600 micrograms/ml) strong dose dependent lipid peroxidation, up to 17.01 nmoles/ml was induced. Under identical conditions, lipid peroxidation induced by up to 600 micrograms/ml ofloxacin, sparofloxacin or lomefloxacin were 0.94, 3.36 and 2.98 nmoles/ml respectively. The lipid peroxidation was entirely dependent on both UV as well as the drug. The lipid peroxidation responses to drug+UV could completely be inhibited by sodium azide (hydroxyl radical, HO. and single oxygen, 1O2 scavenger) or by phenyl N-tert-butylnitrone (PBN, HO. and superoxide anion radical, O2- scavenger). It is likely that reactive oxygen species generated by interaction between UV-sensitized drug molecules and oxygen molecules mediate erythrocyte membrane lipid peroxidation. The method used in this study is rapid and convenient for screening drugs for UV-dependent cytotoxicity.

• Authors: K Wada, A R Saniabadi, K Umemura, Y Takiguchi, M Nakashima
• Journal: Pharmacology & toxicology (Pharmacol Toxicol) 1994 Apr-May Vol. 74 Issue 4-5 Pg. 240-3 ISSN: 0901-9928 [Print] Denmark
• PMID: 8090693 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 4-Quinolones
• Anti-Infective Agents
• Azides
• Cyclic N-Oxides
• Free Radical Scavengers
• Nitrogen Oxides
• Quinolones
• Reactive Oxygen Species
• Thiobarbituric Acid Reactive Substances
• Y 26611
• phenyl-N-tert-butylnitrone
• Sodium Azide

Topics

• 4-Quinolones
• Anti-Infective Agents (antagonists & inhibitors, radiation effects, toxicity)
• Azides (pharmacology)
• Cyclic N-Oxides
• Dose-Response Relationship, Drug
• Erythrocyte Membrane (drug effects)
• Free Radical Scavengers
• Humans
• Lipid Peroxidation (drug effects)
• Male
• Nitrogen Oxides (pharmacology)
• Quinolones (antagonists & inhibitors, radiation effects, toxicity)
• Reactive Oxygen Species
• Sodium Azide
• Thiobarbituric Acid Reactive Substances (analysis)
• Time Factors
• Ultraviolet Rays