title: Cytotoxicity analysis of alendronate on cultured endothelial cells and subcutaneous tissue. a pilot study.
abstract: The use of alendronate, a bisphosphonate which is able to inhibit bone resorption, in order to prevent dental root resorption after tooth replantation would be of clinical relevance. However, this drug must be biocompatible to the periapical tissues. The aim of this study was to analyze the effect of an alendronate paste in polyethyleneglycol (2 g ml(-1)) on endothelial cells in culture (in vitro) and on rat subcutaneous tissue (in vivo). For the in vitro study the paste was applied on round glass coverslips that were immersed into confluent cell cultures (clone Cips). The cell viability percentages of these cultures were obtained 0, 6 and 12 h after contact with the substance. As control, cultures that received plain coverslips were used. This analysis was carried out in triplicate using the Trypan blue dye exclusion assay. For the in vivo study the paste was introduced into polyethylene tubes that were placed into the rat subcutaneous tissue. The rats were killed 7 and 14 days later; then, the tissue sections stained with hematoxylin-eosin were analyzed. In vitro, the alendronate caused a significant decrease in the cell viability in 6 h (P < 0.05) and 12 h (P < 0.01), when compared with the control cultures. In vivo the tissue response was exuberant and similar at the two experimental times. There was a necrosis in a comprehensive area in contact with the open end of the tube. Presence of micro-abscesses and intense inflammatory infiltrate in the hypoderm permeating the muscle fibers and fat lobules were observed. In conclusion, the alendronate paste in polyethylene glycol as used showed to be highly cytotoxic in vitro as well as in vivo.
authors.affiliation: Department of Endodontics, School of Dentistry, University of São Paulo, São Paulo, Brazil.
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Moreira
authors.forename: Emilio
authors.initials: E
authors.lastname: Katayama
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Bombana
authors.forename: Márcia Martins
authors.initials: MM
authors.lastname: Marques
mesh_terms: D019386:Alendronate / Q000009:adverse effects*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D042783:Endothelial Cells / Q000187:drug effects*; D010865:Pilot Projects; D051381:Rats; D040521:Subcutaneous Tissue / Q000187:drug effects*
chemical_list: D050071:Bone Density Conservation Agents; D019386:Alendronate