Effect of antioxidants, anti-inflammatory drugs, and histamine antagonists on sparfloxacin-induced phototoxicity in mice.
We examined the effects of antioxidants, anti-inflammatory drugs, and histamine antagonists on auricular inflammation and retinal degeneration induced by the phototoxicity of sparfloxacin (SPFX), a quinolone antibacterial agent. Catalase (CAT), dimethyl sulfoxide (DMS0), dexamethasone (DM), indomethacin (IM), phenidone (PD), AA-861 (AA), pyrilamine maleate (PY), or cimetidine (CM) was continuously administered to female Balb/c mice using microosmotic pumps for 72 hr and intraperitoneally once before SPFX administration. The mice were given a single oral administration of 50 or 100 mg/kg SPFX and irradiated with ultraviolet-A (UVA) light at 1.5 mW/cm(2) for 4 hr. SPFX administration plus UVA irradiation induced thickening and inflammation of the auricular skin and retinal degeneration in the eye. CAT and DMS0 significantly inhibited the auricular thickening only 4 hr after SPFX administration. DM, IM, and PD also inhibited this toxicity from 4 to 48 or 72 hr. On the other hand, PY and CM showed no effect on this change. With regard to the eye, CAT and DMSO completely inhibited the occurrence of retinal degeneration and IM and PD tended to decrease its incidence, whereas DM, AA, PY, and CM showed no or an exacerbating effect. These results suggest that reactive oxygen species contribute to the initiation of auricular inflammation and retinal degeneration and that cyclooxygenase products are also involved in the initiation and later progression of auricular inflammation. They also show that histamine and 5-lipoxygenase products are not involved in either phototoxic lesion.
Shimoda
K
K
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo, Japan.
Nomura
M
M
Kato
M
M
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000502:physiology; D017484:Dermatitis, Phototoxic / Q000473:pathology; D005260:Female; D024841:Fluoroquinolones; D006633:Histamine Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010787:Photosensitivity Disorders / Q000139:chemically induced* / Q000473:pathology; D015363:Quinolones / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000502:physiology; D012162:Retinal Degeneration / Q000139:chemically induced / Q000473:pathology; D012867:Skin / Q000473:pathology; D014466:Ultraviolet Rays
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D024841:Fluoroquinolones; D006633:Histamine Antagonists; D015363:Quinolones; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; C061363:sparfloxacin