Cytological and cytogenetic effects of the fluoroquinolone ofloxacin on human periodontal ligament fibroblasts.
The fluoroquinolone ofloxacin (OFLX) is one of the candidates of antibacterial agents to be topically used against periodontitis. To estimate the maximum concentration of OFLX which exerts little or no adverse effect on the periodontal ligament, cytological and cytogenetic effects of OFLX on human periodontal ligament fibroblasts (Pel cells) were examined. Treatment of Pel cells with < or =0.3 mM OFLX for 24 or 48 h had little inhibitory effect on cellular growth and survival. DNA, RNA and protein syntheses in Pel cells did not decrease in response to treatment with < or =0.3 mM OFLX. The constitutive level of alkaline phosphatase mRNA was retained in cells treated with < or = 0.03 mM OFLX for 24 or 48 h. The level of type I procollagen mRNA was not affected by treatment with < or = 0.003 mM OFLX for 24 or 48 h. Cytogenetic effects of OFLX were evaluated by the ability of OFLX to induce chromosome aberrations in Pel cells. Treatment with OFLX at 0.3-3.0 mM for 6, 24, or 48 h failed to induce chromosome aberrations in Pel cells. The failure of OFLX to induce chromosome aberrations was seen even in the presence of exogenous metabolic activation using a 5% rat liver post-mitochondrial supernatant mixture. These results indicate that treatment of Pel cells with < or =0.003 mM OFLX has few or no adverse effects on the cytological and cytogenetic endpoints examined, suggesting that there would be little adverse effect on growth and differentiation of the periodontal ligament, as well as little cytogenetic activity, if OFLX were to be topically administered to the gingival crevice at the minimal inhibitory concentration (MIC90) against periodontopathic bacteria (< or = 0.0027 mM). It is important to note, however, that extrapolation of these findings to in vivo conditions has yet to be undertaken.
Someya
T
T
Department of Pharmacology, The Nippon Dental University, School of Dentistry at Tokyo, Japan.
Tamura
Y
Y
Tsutsui
T
T
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000890:Anti-Infective Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D019055:No-Observed-Adverse-Effect Level; D015242:Ofloxacin / Q000633:toxicity*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D011347:Procollagen / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis
D000890:Anti-Infective Agents; D011347:Procollagen; D012333:RNA, Messenger; D004247:DNA; D015242:Ofloxacin; D000469:Alkaline Phosphatase