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Quantitative comparison of the cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts
Author(s) -
Maizumi Noriko,
Tamura Yukiko,
Kanai Hideaki,
Tsutsui Takeki
Publication year - 2002
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1034/j.1600-0765.2002.01616.x
Subject(s) - roxithromycin , josamycin , azithromycin , antibiotics , clarithromycin , microbiology and biotechnology , pharmacology , chemistry , erythromycin , biology
The cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts (Pel cells) was studied. Pel cells were exposed for 48 h to erythromycin (EM), clarithromycin (CAM), roxithromycin (RXM), azithromycin (AZM), josamycin (JM), midecamycin (MDM), and rokitamycin (RKM), and allowed to form colonies. The cytocidal effect of the macrolides was measured as a decrease in colony‐forming efficiency and was found to increase with the concentration. To obtain a quantitative measure of the cytocidal effect, the LD 50 , i.e. the concentration that decreases colony‐forming efficiency 50% relative to control cells, was extrapolated from the concentration‐response curves. The rank of the macrolides according to their cytocidal effect (LD 50 ) was RKM > RXM > CAM > AZM > JM > MDM ≈ EM. RKM, RXM, CAM, AZM, and JM were at least 1.7–12.2 times more cytocidal than MDM or EM. When extrapolated from the concentration‐response curves, the relative survival of the Pel cells exposed to each of the macrolides at the MIC 90 concentrations for periodontopathic bacteria was estimated to be: ≥ 53.8% for RKM, ≥ 92.7% for RXM, ≥ 94.6% for CAM, ≥ 97.1% for AZM, and ≥ 86.2% for EM. The effect of the antibiotics on the mRNA expression of alkaline phosphatase (ALP) and type I procollagen (COL) was examined in Pel cells exposed for 48 h to RXM, CAM, AZM, and EM, which exhibited strong, moderate, and weak cytocidal activity. The constitutive levels of both ALP and COL mRNA were retained in cells exposed to RXM at ≤3 μM, CAM at ≤10 μM, and AZM or EM at ≤3 μM. The MIC 90 against periodontopathic bacteria is ≤4.8 μM for RXM, 5.3 μM for CAM, 2.7 μM for AZM, and 21.8 μM for EM. These results suggest that topical administration of CAM or AZM to the gingival crevice at their MIC 90 concentration for periodontopathic bacteria would have little adverse effect on the growth and differentiation of the periodontal ligament. It is important to note, however, that these findings have yet to be extrapolated to in vivo conditions.