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Photochem Photobiol ; 88(2): 344-55, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22211524

RESUMO

Levofloxacin (LVFX) is a broad spectrum third generation fluoroquinolone antibiotic, used in the treatment of severe or life-threatening bacterial infections. Photosensitizing mechanism of LVFX was investigated under the ambient environmental intensities of UV-A, UV-B and sunlight exposure. Phototoxic effects of LVFX were assessed on NIH-3T3 and HaCaT cell lines. Results identified first time three photoproducts of LVFX at ambient levels of UV-R by LC-MS/MS. The generation of reactive oxygen species (ROS) was investigated photochemically as well as intracellularly in HaCaT cell line. ROS were significantly quenched by specific quenchers like DABCO, NaN(3), D-mannitol and NAC. Photosensitized LVFX caused lipid peroxidation at different concentrations. Quenching study with superoxide dismutase confirms the LVFX-induced lipid photoperoxidation. Further, photocytotoxicity of LVFX showed significant reduction in cell viability by MTT and neutral red uptake assays. LVFX caused cell arrest in G2/M phases as well as induced apoptosis through ROS-dependent pathway. In addition, photosensitized LVFX also induced upregulation of p21 and Bax/Bcl-2 genes ratio. India is a tropical country and most of the human activities such as agriculture, commerce, sports, etc. take place in bright sunlight; therefore, photosensitive LVFX may lead to skin/ocular disorders and immune suppression. Information is needed regarding the phototoxicity of LVFX for human safety.


Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Levofloxacino , Ofloxacino , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Sequestradores de Radicais Livres/farmacologia , Humanos , Queratinócitos/efeitos da radiação , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Ofloxacino/efeitos adversos , Ofloxacino/química , Ofloxacino/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Luz Solar , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/metabolismo , Raios Ultravioleta , Regulação para Cima , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismo
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