As titanium dioxide (TiO(2)) nanoparticles are widely used commercially, the potential effects of TiO(2) nanoparticles on humans are a concern. To evaluate the effects of TiO(2) nanoparticles on hepatic and renal functions and correlate changes to oxidative stress, Sprague-Dawley rats were treated with TiO(2) particles of two different specific surface areas (TiO(2-S50): 50 m(2)/g, and TiO(2-S210): 210 m(2)/g) at 0.5, 5, or 50 mg/kg body weight by intratracheal instillation. After 7 d, TiO(2) nanoparticles produced no obvious acute toxicity on hepatic and renal functions. However, superoxide dismutase (SOD) activity of plasma and glutathione peroxidase (GSH-PX) activity of kidney in the low-dose TiO(2-S210) group were significantly decreased. After TiO(2-S210) exposure, malondialdehyde (MDA) levels of liver and kidney in intermediate and high-dose groups were significantly increased. This change only appeared in liver after TiO(2-S50) exposure. Furthermore, SOD activity in liver and kidney and GSH-PX activity in kidney with low TiO(2-S210) exposure group were significantly less than with low TiO(2-S50). No apparent pathological changes in liver and kidney were observed. Intratracheal exposure to TiO(2) nanoparticles may induce oxidative stress in liver and kidney, but does not influence hepatic or renal functions. There was no apparent evidence that TiO(2-S210) was more toxic than TiO(2-S50). In general, intratracheal exposure to TiO(2) did not markedly affect extrapulmonary tissue functions.

Oxidative stress plays an important role in the progression of Alzheimer's disease (AD) and other neurodegenerative conditions. Glutathione (GSH), the major antioxidant in the central nervous system, is primarily synthesized and released by astrocytes. We determined if β-amyloid (Aβ42), crucially involved in Alzheimer's disease, affected GSH release. Monomeric Aβ (mAβ) stimulated GSH release from cultured cortical astrocytes more effectively than oligomeric Aβ (oAβ) or fibrillary Aβ (fAβ). Monomeric Aβ increased the expression of the transporter ABCC1 (also referred to as MRP1) that is the main pathway for GSH release. GSH release from astrocytes, with or without mAβ stimulation, was reduced by pharmacological inhibition of ABCC1. Astrocytes robustly express connexin proteins, especially connexin43 (Cx43), and mAβ also stimulated Cx43 hemichannel-mediated glutamate and GSH release. Aβ-stimulation facilitated hemichannel opening in the presence of normal extracellular calcium by reducing astrocyte cholesterol level. Aβ treatment did not alter the intracellular concentration of reduced or oxidized glutathione. Using a mouse model of AD with early onset Aβ deposition (5xFAD), we found that cortical ABCC1 was significantly increased in temporal register with the surge of Aβ levels in these mice. ABCC1 levels remained elevated from 1.5 to 3.5 months of age in 5xFAD mice, before plunging to subcontrol levels when amyloid plaques appeared. Similarly, in cultured astrocytes, prolonged incubation with aggregated Aβ, but not mAβ, reduced induction of ABCC1 expression. These results support the hypothesis that in the early stage of AD pathogenesis, less aggregated Aβ increases GSH release from astrocytes (via ABCC1 transporters and Cx43 hemichannels) providing temporary protection from oxidative stress which promotes AD development.

Recent results in our group demonstrated that K n C 60 (n ) 3), a much-studied superconductor and molecular metal, can be encapsulated in the channels of mesoporous niobium oxide to make pseudo-one-dimensional alkali fulleride wires. The oxidation state of the encapsulated fulleride phase can be tuned by addition of potassium naphthalene to the mesostructured composite. Surprisingly, the conductivity of this series of composites has maxima at n ) 2.6 and n ) 4.1, rather than n ) 3 as in the bulk material. In this work, we report a study on the effect of changing the pore size and wall composition of the mesoporous host lattice on the conductivity and electronic behavior of the corresponding potassium fulleride composites. Samples of mesoporous niobium oxide with a 32-Å pore size, mesoporous tantalum oxide with a 22-Å pore size, and mesoporous titanium oxide with a 22-Å pore size were treated with K 3 C 60 and characterized by elemental analysis, nitrogen adsorption, X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), electron spin resonance spectroscopy (ESR), and superconducting quantum interference device (SQUID) magnetometry. These materials were then further reduced with small aliquots of potassium naphthalene in sequential steps up to a fulleride oxidation state of n ) 4.5, and each material was fully characterized as described above. For each series of materials, two conductivity maxima were observed, the first at approximately n ) 2.5 and the second at roughly n ) 4.0, indicating that this double-maxima behavior is general to other onedimensional alkali fulleride mesostructures. There was no clear pattern in the effect of changing pore size and wall composition on the electronic properties; however, all materials near n ) 4.0 showed a greater degree of reduction of the mesostructure and a greater density of states near the Fermi level as determined by XPS, consistent with the high levels of conductivity of the fulleride at this oxidation state.