Ultrathin TiO2 Coatings via Atomic Layer Deposition Strongly Improve Cellular Interactions on Planar and Nanotubular Biomedical Ti Substrates.

This work aims to investigate the chemical and/or structural modification of Ti and Ti-6Al-4V (TiAlV) alloy surfaces to possess even more favorable properties toward cell growth. These modifications were achieved by (i) growing TiO2 nanotube layers on these substrates by anodization, (ii) surface coating by ultrathin TiO2 atomic layer deposition (ALD), or (iii) by the combination of both. In particular, an ultrathin TiO2 coating, achieved by 1 cycle of TiO2 ALD, was intended to shade the impurities of F- and V-based species in tested materials while preserving the original structure and morphology. The cell growth on TiO2-coated and uncoated TiO2 nanotube layers, Ti foils, and TiAlV alloy foils were compared after incubation for up to 72 h. For evaluation of the biocompatibility of tested materials, cell lines of different tissue origin, including predominantly MG-63 osteoblastic cells, were used. For all tested nanomaterials, adding an ultrathin TiO2 coating improved the growth of MG-63 cells and other cell lines compared with the non-TiO2-coated counterparts. Here, the presented approach of ultrathin TiO2 coating could be used potentially for improving implants, especially in terms of shading problematic F- and V-based species in TiO2 nanotube layers.

Cysteine conjugates of acetaminophen and p-aminophenol are potent inducers of cellular impairment in human proximal tubular kidney HK-2 cells.

Acetaminophen (APAP) belong among the most used analgesics and antipyretics. It is structurally derived from p-aminophenol (PAP), a potent inducer of kidney toxicity. Both compounds can be metabolized to oxidation products and conjugated with glutathione. The glutathione-conjugates can be cleaved to provide cysteine conjugates considered as generally nontoxic. The aim of the present report was to synthesize and to purify both APAP- and PAP-cysteine conjugates and, as the first study at all, to evaluate their biological effects in human kidney HK-2 cells in comparison to parent compounds. HK-2 cells were treated with tested compounds (0-1000 µM) for up to 24 h. Cell viability, glutathione levels, ROS production and mitochondrial function were determined. After 24 h, we found that both APAP- and PAP-cysteine conjugates (1 mM) were capable to induce harmful cellular damage observed as a decrease of glutathione levels to 10% and 0%, respectively, compared to control cells. In addition, we detected the disappearance of mitochondrial membrane potential in these cells. In the case of PAP-cysteine, the extent of cellular impairment was comparable to that induced by PAP at similar doses. On the other hand, 1 mM APAP-cysteine induced even larger damage of HK-2 cells compared to 1 mM APAP after 6 or 24 h. We conclude that cysteine conjugates with aminophenol are potent inducers of oxidative stress causing significant injury in kidney cells. Thus, the harmful effects cysteine-aminophenolic conjugates ought to be considered in the description of APAP or PAP toxicity.