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Comparative effects of two bisphosphonates (clodronate and zk 90695) on Hydroxyapatite-Rimed human neutrophil chemiluminescence

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Kowolik MJ, Hyvönen PM. Comparative effects of two bisphosphonates (clodronate and ZK 90695) on hydroxyapatite-primed human neutrophil chemiluminescence. Inflammopharmacology. 1994;2:369-376.

An established in-vitro model was applied to study the interaction between human neutrophil granulocytes, hydroxyapatite particles (HA) and two bisphosphonate drugs, dichloromethylene bisphosphonate (clodronate), and ZK 90695, an experimental agent. Luminol- and lucigenin-mediated chemiluminescence (CL) assays were used to monitor activation in the oxygen-dependent pathway. Little effect was seen by either drug over a concentration range of 1 × 10s-13 to 1 × 10s-5 mol/L, in the absence of HA, when the cells were subjected to a second challenge of serum-treated zympsan or phorbol myristate acetate (PMA). Although beyond the therapeutic range, only at 1 × 10s-3 mol/L was cell activity abolished as confirmed by trypan blue dye exclusion. Preincubation of neutrophils with serum-coated HA produced a typical priming for the second stimulus but binding of either drug to the mineral particles had minimal effect on priming except at the highest concentrations of 1 × 10s-4 and 1 × 10s-3 mol/L. These results support our findings regarding the low toxicity of clodronate in this experimental assay, and provide similar evidence for the experimental bisphosphonate, ZK 90695. In addition to the established use of bisphosphonates, there is increasing interest in studying their anti-inflammatory effects, to which this model is well-suited.

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Authors and Affiliations

  1. Department of Periodontology, Leeds Dental Institute, Clarendon Way, LS2 9LU, Leeds, UK

    M. J. Kowolik

  2. Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland

    P. M. Hyvönen

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  1. M. J. Kowolik
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  2. P. M. Hyvönen
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Kowolik, M.J., Hyvönen, P.M. Comparative effects of two bisphosphonates (clodronate and zk 90695) on Hydroxyapatite-Rimed human neutrophil chemiluminescence. Inflammopharmacology 2, 369–376 (1994). https://doi.org/10.1007/BF02678603

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