Important role of oxygen metabolites in quinolone antibacterial agent-induced cutaneous phototoxicity in mice.
We investigated whether or not the generation of reactive oxygens and toxic photoproducts participated in the cutaneous phototoxicity mechanisms induced by the quinolone derivatives, ofloxacin (OFLX), enoxacin, lomefloxacin, ciprofloxacin and DR-3355 (the s-isomer of OFLX) in a mouse model. Pretreatment of Balb/c mice with allopurinol, soybean trypsin inhibitor, catalase and beta-carotene gave significant protection against ear swelling reactions induced by oral administration of quinolones and following ultraviolet-A (UVA) irradiation. Pretreatment with diethyldithiocarbamate augmented the swelling. No swelling was observed with direct injection into the auricle of UVA-pretreated photoproducts of the quinolones. These results showed that cutaneous phototoxicity did not depend on the generation of toxic photoproducts and suggested that oxygen metabolites generated in the xanthine oxidase pathway participated in the toxicity.
Wagai
N
N
Research Institute, Daiichi Pharmaceutical Co., Ltd, Tokyo, Japan.
Tawara
K
K
D042462:4-Quinolones; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D002338:Carotenoids / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000378:metabolism*; D010787:Photosensitivity Disorders / Q000139:chemically induced*; D012867:Skin / Q000528:radiation effects; D014361:Trypsin Inhibitors / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects; D019207:beta Carotene
D042462:4-Quinolones; D000890:Anti-Infective Agents; D014361:Trypsin Inhibitors; D019207:beta Carotene; D002338:Carotenoids; D000493:Allopurinol; D004050:Ditiocarb; D002374:Catalase; D010100:Oxygen