Bioactive glasses such as Hench's 45S5 (Bioglass®) have applications to tissue engineering aswell as bone repair, and the insertion of fluoride in their composition has been proposed to enhancetheir bioactivity. In view of a potential clinical application, we investigated whether fluoride-containingglasses exert toxic effects on human MG-63 osteoblasts, and whether and how fluoride, which isreleased in the cell culture medium, might play a role in such cytotoxicity. A 24 h incubation with 50μg/ml (12.5 μg /cm2) of fluoride-containing bioactive glasses termed HCaCaF2 (F content: 5, 10 and15% mol) caused the release of lactate dehydrogenase in the extracellular medium (index ofcytotoxicity), the accumulation of intracellular malonyldialdehyde (index of lipoperoxidation), and theincrease of glutathione consumption. Furthermore, fluoride-containing glasses inhibited the pentosephosphate oxidative pathway and the glucose 6-phosphate dehydrogenase activity. These effects areascribable to the fluoride content/release of glass powders, since they were mimicked by NaF solutionsand were prevented by dimethyl sulfoxide and tempol (two radical scavengers), by superoxidedismutase (a superoxide scavenger), and by glutathione (the most important intracellular antioxidantmolecule), but not by apocynin (an inhibitor of NADPH oxidase). The presence of fluoride-containingglasses and NaF caused also the generation of reactive oxygen species, which was prevented bysuperoxide dismutase and catalase. The data suggest that fluoride released from glasses is the cause ofMG-63 cell oxidative damage and is independent of NADPH oxidase activation. Our data provide a newmechanism to explain F ̅ ions toxicity: fluoride could trigger, at least in part, an oxidative stress viainhibition of the pentose phosphate oxidative pathway and, in particular, through the oxidativeinhibition of glucose 6-phosphate dehydrogenase.

Fluoride-containing bioactive glasses inhibit pentose phosphate oxidative pathway and glucose 6-phosphate dehydrogenase activity in human osteoblasts / Bergandi, L.; Aina, V.; Malavasi, Gianluca; Aldieri, E.; Laurenti, E.; Morterra, C.; Ghigo, D.. - In: CHEMICO-BIOLOGICAL INTERACTIONS. - ISSN 0009-2797. - STAMPA. - 183 (3):(2010), pp. 1405-1415. [10.1016/j.cbi.2009.11.021]

Fluoride-containing bioactive glasses inhibit pentose phosphate oxidative pathway and glucose 6-phosphate dehydrogenase activity in human osteoblasts

MALAVASI, Gianluca;
2010-01-01

Abstract

Bioactive glasses such as Hench's 45S5 (Bioglass®) have applications to tissue engineering aswell as bone repair, and the insertion of fluoride in their composition has been proposed to enhancetheir bioactivity. In view of a potential clinical application, we investigated whether fluoride-containingglasses exert toxic effects on human MG-63 osteoblasts, and whether and how fluoride, which isreleased in the cell culture medium, might play a role in such cytotoxicity. A 24 h incubation with 50μg/ml (12.5 μg /cm2) of fluoride-containing bioactive glasses termed HCaCaF2 (F content: 5, 10 and15% mol) caused the release of lactate dehydrogenase in the extracellular medium (index ofcytotoxicity), the accumulation of intracellular malonyldialdehyde (index of lipoperoxidation), and theincrease of glutathione consumption. Furthermore, fluoride-containing glasses inhibited the pentosephosphate oxidative pathway and the glucose 6-phosphate dehydrogenase activity. These effects areascribable to the fluoride content/release of glass powders, since they were mimicked by NaF solutionsand were prevented by dimethyl sulfoxide and tempol (two radical scavengers), by superoxidedismutase (a superoxide scavenger), and by glutathione (the most important intracellular antioxidantmolecule), but not by apocynin (an inhibitor of NADPH oxidase). The presence of fluoride-containingglasses and NaF caused also the generation of reactive oxygen species, which was prevented bysuperoxide dismutase and catalase. The data suggest that fluoride released from glasses is the cause ofMG-63 cell oxidative damage and is independent of NADPH oxidase activation. Our data provide a newmechanism to explain F ̅ ions toxicity: fluoride could trigger, at least in part, an oxidative stress viainhibition of the pentose phosphate oxidative pathway and, in particular, through the oxidativeinhibition of glucose 6-phosphate dehydrogenase.
183 (3)
1405
1415
Fluoride-containing bioactive glasses inhibit pentose phosphate oxidative pathway and glucose 6-phosphate dehydrogenase activity in human osteoblasts / Bergandi, L.; Aina, V.; Malavasi, Gianluca; Aldieri, E.; Laurenti, E.; Morterra, C.; Ghigo, D.. - In: CHEMICO-BIOLOGICAL INTERACTIONS. - ISSN 0009-2797. - STAMPA. - 183 (3):(2010), pp. 1405-1415. [10.1016/j.cbi.2009.11.021]
Bergandi, L.; Aina, V.; Malavasi, Gianluca; Aldieri, E.; Laurenti, E.; Morterra, C.; Ghigo, D.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/634819
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