Studies on experimental conditions for detecting phototoxic potentials of drugs in balb/c mice.

Wagai, Nobuhiko; Fumie, Yamaguchi; Tawara, Katsuhiko; Onodera, Toshiyuki

doi:10.2131/jts.14.197

Cited by 20 publications

(6 citation statements)

References 13 publications

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“…However, LVFX induced marked and very slight changes in the auricle at 800 and 400 mg/kg, respectively, but induced no retinal changes at either dose. LVFX is therefore thought to possess less potent phototoxicity than ENX and SPFX, a finding supported by previous data in the thickness changes of auricles (36,38).…”

Section: Discussionsupporting

confidence: 79%

Phototoxic Lesions Induced by Quinolone Antibacterial Agents in Auricular Skin and Retina of Albino Mice

et al. 1993

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The phototoxic effects of quinolone antimicrobial agents on mouse auricular skin and retina were examined histologically. Sparfloxacin at 50 or 100 mg/kg, which alone causes no histologic change, was orally administered to albino Balb/c mice, which were irradiated with ultraviolet A for 4 hr immediately after administration. In the auricle, degeneration of basal epidermal cells was sporadically observed at 2 hr (during the irradiation). Foci of slight edema with degenerated fibroblasts were seen in the dermis at 4 hr. Edema and neutrophil infiltration in the dermis became severe up to 96 hr. Initial changes in the retina were observed at 2 hr. Vacuolation of the photoreceptor segments (particularly the inner segment) was occasionally associated with swelling of retinal pigment epithelial cells. The segments became disorganized with time, and the outer nuclear layer showed reduced cellularity. The segments and layer were partially thinned and lost 96 hr later. Enoxacin at 400 and 800 mg/kg induced similar lesions to those of sparfloxacin. Levofloxacin caused similar lesions in the auricle but no change in the retina. The combination of oral administration of quinolone and ultraviolet A irradiation, which never caused apparent morphological changes alone, was shown to be able to induce phototoxic lesions in albino mice. Therefore, this method is thought to be useful to examine morphological changes caused by quinolone phototoxicity.

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Section: Discussionsupporting

confidence: 79%

Phototoxic Lesions Induced by Quinolone Antibacterial Agents in Auricular Skin and Retina of Albino Mice

et al. 1993

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“…Details of the light source and of the method of irradiation have been described previously (Wagai et al 1989). Briefly, the light source consisted of a bank of ten Toshiba FL20SBLB "Black Light" tubes, emitting radiation on a wavelength range of 300-400 nm.…”

Section: Methodsmentioning

confidence: 99%

Important role of oxygen metabolites in quinolone antibacterial agent-induced cutaneous phototoxicity in mice

Wagai

Tawara

1991

Arch Toxicol

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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.

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“…Furthermore, introduction of a methoxy group to the 8 position effectively reduces phototoxicity. Wagai et al (1989Wagai et al ( , 1990) compared the phototoxicity of many quinolones in albino BALB/c mice using a method in which doses of a quinolone and Downloaded by [North Carolina State University] at 13:18 14 October 2012 UVA irradiation that induced no change in the auricle when given alone induced erythema and thickening of the auricle upon single oral administration of the quinolone followed by irradiation for 4 h. By this method, the order of toxic potential was lomefloxacin > enoxacin, nalidixic acid > ofloxacin, levofloxacin, ciprofloxacin. The authors considered that this order reflects the toxic potential of these drugs in humans.…”

Section: Phototoxicitymentioning

confidence: 99%

Toxicity of quinolone antimicrobial agents

Takayama¹,

Hirohashi²,

Kato³

et al. 1995

Journal of Toxicology and Environmental Health

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An approach to minimization of toxicity of a new compound is to elucidate the mechanisms of toxicity of analogous compounds and to clarify their structure-toxicity relationships. A problem with this approach, however, is that such elucidation remains difficult. For quinolones, some improvements in this mechanistic approach have been achieved in the central nervous system (CNS), particularly with regard to their interaction with non-steroidal anti-inflammatory drugs (NSAIDs), and in genotoxicity and phototoxicity studies, particularly in comparison with other toxicities, such as to the cardiovascular, gastrointestinal, bone, reproductive, and developmental systems. This review concentrates on a description of the known effects of quinolones on various organ systems in experimental animals and humans. Given the logarithmic increase in the synthesis of new quinolones, it is questionable whether these drugs share similar safety and efficacy. Nevertheless, this mechanistic approach to the investigation and minimization of toxicity has produced satisfactory results to date and deserves to be continued.

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Studies on experimental conditions for detecting phototoxic potentials of drugs in balb/c mice.

Cited by 20 publications

References 13 publications

Phototoxic Lesions Induced by Quinolone Antibacterial Agents in Auricular Skin and Retina of Albino Mice

Phototoxic Lesions Induced by Quinolone Antibacterial Agents in Auricular Skin and Retina of Albino Mice

Important role of oxygen metabolites in quinolone antibacterial agent-induced cutaneous phototoxicity in mice

Toxicity of quinolone antimicrobial agents

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