Quinolone antibacterial-agent-induced cutaneous phototoxicity: ear swelling reactions in Balb/c mice.
The phototoxic potentials of quinolone derivatives and the possibility of free radical contribution to their phototoxicity were investigated by measuring increments in ear thickness. Balb/c mice, fasted overnight, were orally administered ofloxacin (OFLX), lomefloxacin (LMFX), enoxacin (ENX), ciprofloxacin (CPFX) and DR-3355 (the s-isomer of OFLX), and immediately exposed to ultraviolet-A light (UVA: 320-400 nm) for 4 h (21.6 joules/cm2). Measurement of ear thickness was carried out 0, 24 and 48 h after the end of irradiation. The time-course profiles of ear thickness varied with both the doses and the quinolone used, but linear dose-response curves were obtained from the data 24 h after irradiation ended. The 50% ear thickness increment-inducing doses of LMFX, ENX, OFLX, CPFX and DR-3355 were calculated as 24.8, 81.9, 428.0, 457.9 and 526.6 mg/kg, respectively. The phototoxic potential of these quinolones coincided with the data obtained previously by measuring the incidence of erythema on the ears. Pretreatment with butylated hydroxtoluene, a free radical scavenger, almost completely prevented all swelling reactions induced by the quinolones. These results suggest that the degree of phototoxicity induced by the quinolones used could depend on the balance between the generation of free radicals and the effectiveness of the defense systems against toxic radicals.
Wagai
N
N
Developmental Research Laboratories, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Tawara
K
K
D042462:4-Quinolones; D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004427:Ear Diseases / Q000139:chemically induced; D004487:Edema / Q000139:chemically induced; D005260:Female; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010777:Photochemistry; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D013997:Time Factors; D014466:Ultraviolet Rays
D042462:4-Quinolones; D000890:Anti-Infective Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D002084:Butylated Hydroxytoluene