title: In vitro biological effects of sodium titanate materials.
abstract: Monosodium titanate (MST) particles effectively bind specific metals and are therefore promising compounds for delivery or sequestration of metals in biological contexts. Yet, the biological properties of MST are largely unexplored. Our previous study showed that the cytotoxicity of these compounds was mild, but the nature of the dose response curves suggested that residual titanates in culture may have interfered with the assay. In the current study, we assessed the importance of these artifacts, and extended our previous results using fibroblasts for biological evaluation. We also assessed the biological response to a new type of titanate (referred to as amorphous peroxo-titanate or APT) that shows more promising metal binding properties than MST.
  
  
  METHODS
  The degree of titanate-induced interference in the MTT (mitochondrial activity assay) was estimated by means of cell-free assays with and without a final centrifugation step to remove residual titanate particulate. Cytotoxic responses to titanates were assessed by measuring succinate dehydrogenase activity (by MTT) in THP1 monocytes or L929 fibroblasts after 24-72 h exposures. Monocytic activation by APT was assessed by TNFalpha secretion (ELISA) from monocytes with or without lipopolysaccharide (LPS) activation.
  
  
  RESULTS
  We confirmed that residual titanate particulates may alter the SDH activity assay, but that this effect is eliminated by adding a final centrifugation step to the standard MTT procedure. Addition of MST or APT at concentrations up to 100 mg/L altered succinate dehydrogenase activity by < 25% in both monocytes and fibroblasts. Fibroblasts displayed time-dependent adaptation to the MST. APT did not trigger TNFalpha secretion or modulate LPS-induced TNFalpha secretion from monocytes.
  
  
  CONCLUSIONS
  Although further in vitro and in vivo assessment is needed, MST and APT exhibit biological properties that are promising for their use as agents to sequester or deliver metals in biological systems.
authors.affiliation: Medical College of Georgia, Augusta, Georgia 30912-1100, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Davis
authors.forename: P E
authors.initials: PE
authors.lastname: Lockwood
authors.forename: D T
authors.initials: DT
authors.lastname: Hobbs
authors.forename: R L W
authors.initials: RL
authors.lastname: Messer
authors.forename: R J
authors.initials: RJ
authors.lastname: Price
authors.forename: J B
authors.initials: JB
authors.lastname: Lewis
authors.forename: J C
authors.initials: JC
authors.lastname: Wataha
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008422:Materials Testing; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D010087:Oxides / Q000737:chemistry / Q000633:toxicity*; D013385:Succinate Dehydrogenase / Q000032:analysis; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D001672:Biocompatible Materials; D010087:Oxides; D014409:Tumor Necrosis Factor-alpha; C525208:peroxo-titanate; C471701:sodium titanate; D014025:Titanium; D013385:Succinate Dehydrogenase