The aim of this study was to clarify the mechanisms underlying the erythema of guinea pig skin induced by ultraviolet (UV) irradiation alone and in combination with a systemic fluoroquinolone (FQ). The effects of several drugs which may modify the actions of some inflammatory mediators and radicals possibly released in the inflamed site on the erythema were examined and compared in an objective and quantitative way by measuring the change in color of the irradiated skin, determined as the change in chroma (C*) with use of reflectance colorimetry. After confirming that the C* value increased in an irradiation dose-dependent manner and reached a plateau 1-2 h after irradiation of UVB alone or UVA coadministered with an FQ, Y-26611 (10 mg/kg, i.p.), guinea pigs were pretreated with indomethacin, butylated hydroxytoluene (BHT) or beta-carotene before, or treated with H1- or H2-receptor antagonist, superoxide dismutase or N omega-nitro-L- arginine methyl ester after UV irradiation, and their inhibitory effects against erythema were evaluated. It was suggested that there are some substantial differences between UVB- and UVA plus FQ-induced erythemas. Although histamine makes little contribution to both types of erythema, metabolites of arachidonic acid catalyzed by cyclooxygenase contribute more to UVB-induced erythema, whereas superoxides take more part in UVA plus FQ-induced erythema. Furthermore, nitric oxide seems to participate in both types of erythema; however, the pretreatment with BHT or beta-carotene was ineffective against both erythemas. From these results, interventions should be directed to powerfully scavenging radicals for prevention and treatment of UV plus FQ-induced phototoxicity.

01 May 1995·Free Radical Biology and MedicineQ2 · MEDICINE

Direct measurement of superoxide-dependent chemiluminescence from rat skin following UV-dependent fluoroquinolone-induced dermatitis

Q2 · MEDICINE

Article

Author: Nakashima, Mitsuyoshi ; Umemura, Kazuo ; Nakano, Minoru ; Ito, Takashi ; Saniabadi, Abby R. ; Wada, Kouichirou

Fluoroquinolones are widely used for the treatment of bacterial infection. However, some members of the group cause UV-dependent dermatitis. Therefore, animal models are required to screen and predict if a derivative is likely to cause photodermatitis. Under anaesthesia, the hair on the dorsal side of rats was shaved, then a fluoroquinolone derivative, Y-26611 or ofloxacin was administered subcutaneously (SC) followed by irradiation of a 3 cm diameter circular area of the skin with UV-B(ultraviolet-B) for 45 min. Peak photodermatitis was observed 24 h after irradiation in Y-2611-treated skin. Leucocyte infiltration into the skin, mostly polymorphonuclear leucocytes, was verified by histological techniques. O2.- radical generated by activated leucocytes was detected directly from the skin by SC application of a sensitive O2.- -dependent luminescence reagent, MCLA. O2.- -dependent photon emission (chemiluminescence) from the skin was amplified by phorbol myristate acetate and was markedly suppressed by superoxide dismutase. This is the first report of direct detection of chemiluminescence from the skin of a living animal.

01 Jan 1994·ChemotherapyQ4 · MEDICINE

Enhanced Chemiluminescence Response of Polymorphonuclear Leukocytes by New Quinolone Antimicrobials

Q4 · MEDICINE

Article

Author: Tanaka, Masatoshi ; Matsumoto, Tetsuro ; Sakumoto, Misao ; Takahashi, Koichi ; Kubo, Shuta ; Kumazawa, Joichi ; Haraoka, Masashi ; Sakamoto, Yasuki

Some of the many antimicrobial agents (beta-lactams, macrolides, aminoglycosides, tetracyclines, new quinolones; NQs) were reported to have a bactericidal or bacteriostatic effect cooperating with host defense mechanisms including polymorphonuclear neutrophils (PMNs). We investigated the effect of new quinolone antimicrobials on chemiluminescence (CL) response of human PMNs. Among many NQs, we chose ofloxacin, lomefloxacin, fleroxacin, sparfloxacin, AM-1155, NM-394, Q-35, Y-26611 and T-3761. Twenty-five or 100 micrograms/ml of fleroxacin and ofloxacin enhanced luminol-dependent CL response of PMNs up to 1.5-2.0 times compared to the drug free condition. Other antimicrobial agents, however, inhibited CL response. This suggested that fleroxacin and ofloxacin were more efficient in the treatment of bacterial infections with respect to the interaction between antimicrobials and PMNs.

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Indication	Highest Phase	Country/Location	Organization	Date
Bacterial Infections	Phase 2	-	Mitsubishi Tanabe Pharma Corp.	-
Bacterial Infections	Phase 2	-	Japan Tobacco (Hong Kong) Ltd.	-

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