UV-dependent quinolone-induced human erythrocyte membrane lipid peroxidation: studies on the phototoxicity of Y-26611, a new quinolone derivative.
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.
Wada
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Saniabadi
A R
AR
Umemura
K
K
Takiguchi
Y
Y
Nakashima
M
M
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000037:antagonists & inhibitors / Q000528:radiation effects / Q000633:toxicity*; D001386:Azides / Q000494:pharmacology; D003497:Cyclic N-Oxides; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects*; D016166:Free Radical Scavengers; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009589:Nitrogen Oxides / Q000494:pharmacology; D015363:Quinolones / Q000037:antagonists & inhibitors / Q000528:radiation effects / Q000633:toxicity*; D017382:Reactive Oxygen Species; D019810:Sodium Azide; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors; D014466:Ultraviolet Rays
D042462:4-Quinolones; D000890:Anti-Infective Agents; D001386:Azides; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D015363:Quinolones; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C078061:Y 26611; C029217:phenyl-N-tert-butylnitrone; D019810:Sodium Azide