title: Hydrogen peroxide induced stress in human keratinocytes and its effect on bithionol toxicity.
abstract: Exposure to hydrogen peroxide causes oxidative stress in keratinocytes. Previous work has shown that the antiparasitic drug bithionol has an EC(50) of 0.7 microg/ml (2 microM) with primary human keratinocytes, but that these cells do not respond to photoactivated bithionol. Bithionol is known to be photoactivated by UV-A visible light, therefore this study aims to investigate the effects of inducing oxidative stress in the cells prior to bithionol treatment alone and in the presence of UV-A visible light. Oxidative stress, by hydrogen peroxide treatment, caused the cells to become sensitive to photoactivated bithionol. Bithionol alone reduced the amount of oxidative stress, while following photoactivation, an augmentation in the amount of oxidative stress and cell cytotoxicity was observed. The hydrogen peroxide treatment did not alter the sensitivity of the keratinocytes to 5 J/cm(2) UV-A visible light.
authors.affiliation: FRAME Alternatives Laboratory, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK. mbxlr@nottingham.ac.uk
authors.forename: L
authors.initials: L
authors.lastname: Reid
authors.forename: R H
authors.initials: RH
authors.lastname: Clothier
authors.forename: N
authors.initials: N
authors.lastname: Khammo
mesh_terms: D000980:Antiplatyhelmintic Agents / Q000633:toxicity*; D001735:Bithionol / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D010078:Oxazines; D018384:Oxidative Stress / Q000187:drug effects*; D017319:Photosensitizing Agents / Q000633:toxicity; D011506:Proteins / Q000378:metabolism; D014466:Ultraviolet Rays; D014966:Xanthenes
chemical_list: D000980:Antiplatyhelmintic Agents; D004396:Coloring Agents; D010078:Oxazines; D017319:Photosensitizing Agents; D011506:Proteins; D014966:Xanthenes; C005843:resazurin; D001735:Bithionol; D006861:Hydrogen Peroxide