Cytotoxicity of zinc-containing bioactive glasses in contact with human osteoblasts.
Bioactive glasses such as Hench's 45S5 have applications to tissue engineering and bone repair: the insertion of zinc has been proposed to improve their bone-bonding ability and to slacken their dissolution in extracellular body fluids. In view of a potential clinical application, we have investigated whether zinc-containing 45S5 (HZ) glasses might be cytotoxic for human MG-63 osteoblasts. In our experimental conditions, after 24h of incubation HZ glasses released significant amounts of Zn(2+) and induced in MG-63 cells release of lactate dehydrogenase (index of cytotoxicity) and the following indexes of oxidative stress: (i) accumulation of intracellular malonyldialdehyde, (ii) increased activity of pentose phosphate pathway, (iii) increased expression of heme oxygenase-1, (iv) increased activity of Cu,Zn-superoxide dismutase, (v) decreased level of intracellular thiols. These effects were inversely related to the zinc content of glass powders, were mimicked by ZnCl(2) solutions and were prevented by either metal chelators (EDTA, NTA) or the antioxidant ascorbate, suggesting that Zn(2+) released fastly from HZ glasses can cause MG-63 cell damage via an oxidative stress. This work highlights the importance of designing Zn-containing bioactive glasses without cytotoxic effects and gives supplementary information about the prooxidant role of zinc in living systems.
Aina
Valentina
V
Department of Chemistry IFM and Centre of Excellence NIS, University of Torino, Via Giuria 7, 10125 Torino, Italy.
Perardi
Alessandra
A
Bergandi
Loredana
L
Malavasi
Gianluca
G
Menabue
Ledi
L
Morterra
Claudio
C
Ghigo
Dario
D
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002516:Ceramics; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005898:Glass / Q000737:chemistry; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010428:Pentosephosphates / Q000378:metabolism; D019736:Prostheses and Implants; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
D010428:Pentosephosphates; D013438:Sulfhydryl Compounds; C425330:bioactive glass 45S5; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D015032:Zinc