title: Cytotoxicity in ciprofloxacin-treated human fibroblast cells and protection by vitamin E.
abstract: Quinolones (Qs) were shown to have cytotoxic effects in various cell lines including human carcinoma cells; however, mechanism of these effects was not fully understood. To investigate the possibility of the involvement of an oxidative stress induction in this mechanism of action, we examined viability of human fibroblast cells exposed to a Q antibiotic, ciprofloxacin (CPFX), and measured lipid peroxidation and total glutathione (GSH) levels, and activities of catalase (Cat), superoxide dismutases (SODs), glutathione peroxidase (GPx). The effects of vitamin E pretreatment on those parameters were also examined. Our results showed that the effect of CPFX on the viability of the cells, as determined by neutral red uptake assay, was time dependent. Cytotoxicity was not observed in the concentration range of 0.0129-0.387 mM CPFX when the cells were incubated for 24 hours. However, significant level of cytotoxicity was observed at concentrations 0.129 and 0.194 mM, and >0.129 mM, following 48 and 72 hours of exposure, respectively. When the cells were exposed to 0.194 mM CPFX for 48 hours, the level of lipid peroxidation increased and the content of total GSH decreased significantly; activities of total SOD, Mn SOD and CuZn SOD did not change; the decrease observed in the activity of Cat was not significant; and the activity of GPx was highly variable. Vitamin E pretreatment of the cells provided significant protection against CPFX-induced cytotoxicity; lowered the level of lipid peroxidation significantly, but increased the total GSH content only moderately; no change was observed in the activities of Cat and total SOD, but a significant increase in Mn SOD and a significant decrease in CuZn SOD were noticed. These results suggested that CPFX-induced cytotoxicity on human fibroblast cell cultures is related to oxidative stress, and vitamin E pretreatment can afford a protection.
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, University of Hacettepe, Ankara 06100, Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Gürbay
authors.forename: C
authors.initials: C
authors.lastname: Garrel
authors.forename: M
authors.initials: M
authors.lastname: Osman
authors.forename: M J
authors.initials: MJ
authors.lastname: Richard
authors.forename: A
authors.initials: A
authors.lastname: Favier
authors.forename: F
authors.initials: F
authors.lastname: Hincal
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D000975:Antioxidants; D014810:Vitamin E; D002939:Ciprofloxacin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione