Table 3.
Toxic effects of TiO2 NPs on CNS in in vitro studies
| Crystal type | Cell type | Parameters/dose | Main findings | Reference |
|---|---|---|---|---|
| Unknown | Primary microglia from Sprague–Dawley rats and PC12 | 20 nm; 0.25 or 0.5 mg/ml; 24 or 48 h | NO, iNOS, MCP-1, MIP-1α, and NF-κB binding activity increased and Th inhibited in microglia; marked cytotoxicity in PC12 after incubation with supernatant of NPs-treated microglia | [88] |
| Anatase | PC12 | Average 21 nm (range from 20 to 50 nm); 1, 10, 50, 100 μg/ml; incubated for 6, 12, 24, 48 h | Viability of cells decreased except 1 μg/ml group; DCF-positive cells and ratio of PC12 apoptosis elevated | [89] |
| Anatase and rutile | PC12 | 20 nm; 25, 50, 100, 200 μg/ml for 24 h | Apparent cytotoxicity; GSH, SOD, and mitochondrial membrane potential decreased; MDA and G2/M phase cells elevated; p-JNK, JNK, p-c-Jun, Jun, p-P53, p53, p21 GADD45, Bcl-2, and Bax disrupted | [90] |
| Anatase (96 %) | C6 U373 | 40–200 nm; 2.5, 5, 10, 20, 40 μg/ml; 24, 48 or 96 h | Apoptosis; cellular proliferation depressed; morphology and cytoskeleton changed; reduction in immune-location of F-actin fibers | [96] |
| Unknown | C6 U373 | 50 nm; 20 μg/cm2 for 2, 4, 6, 24, 48, 72 h | Imbalance in GPx, SOD and catalase; fluorescence of cis-parinaric acid and Rh123 downregulated; H2DCFDA and MitoTracker Green FM staining elevated | [97] |
| Rutile coated by SiO2 | Mouse NSCs line C17.2 | 80–100 nm; 50, 100, 150, 200, 250 μg/ml exposed for 12, 24, 36, 48, 60, 72 h, or 7 days | Inhibition on cellular proliferation; β-tubulin positive cells detected; Cx43 elevated; PKCε reduced | [99] |
| Unknown | HCECs (human cerebral endothelial cells) | 21 nm; 2 mg/ml; 0.12, 0.6, 3, 15, 75 μg/cm2 for 4, 24, 48, or 72 h | Significant cytotoxicity, ROS production, and marked DNA damage detected; cathepsin D and LC3-II upregulated | [98] |
| Anatase | Primary hippocampal neurons | 5 nm; 5, 15, 30, 40, 50 μg/ml for 6, 12, 24, or 48 h | Cell viabilities and MMP reduced; LDH activities, apoptotic rate, and cytoplasmic Ca2+ elevated; ultrastructure of cells altered; apoptotic cytokine disturbed | [91] |
| Anatase (S) Anatase (80 %) + rutile (D) | Human SHSY5Y neuronal cells | 25 nm; 20, 40, 60, 80, 100, 120, 140, 160 μg/ml for 3, 6, 24 h | No cytotoxicity; cell cycle changed; apoptotic cells elevated; genotoxicity detected; no oxidative damage | [92] |
| Anatase | Human neural stem cell line | 80 nm; 0.01, 0.1, 1 mg/ml for 7 days | Morphology changed; mitochondrial activity not changed; Nestin, neurofilament heavy polypeptide, and high mobility group AT-hook 1 elevated | [100] |