Electronic microscopy evidence for mitochondria as targets for Cd/Se/Te-based quantum dot 705 toxicity in vivo.

The safety of quantum dots (QDs) 705 was evaluated in this study. Mice were treated with QD705 (intravenous) at a single dose of (40 pmol) for 4, 12, 16, and 24 weeks. Effects of QD705 on kidneys were examined. While there was a lack of histopathology, reduction in renal functions was detected at 16 weeks. Electron microscopic examination revealed alterations in proximal convoluted tubule (PCT) cell mitochondria at even much earlier time, including disorientation and reduction of mitochondrial number (early change), mitochondrial swelling, and later compensatory mitochondrial hypertrophy (enlargement mitochondria: giant mitochondria with hyperplastic inner cristae) as well as mitochondrial hyperplasia (increase in mitochondrial biogenesis and numbers) were observed. Such changes probably represent compensatory attempts of the mitochondria for functional loss or reduction of mitochondria in QD705 treated animals. Moreover, degeneration of mitochondria (myelin-figure and cytoplasmic membranous body formation) and degradation of cytoplasmic materials (isolated cytoplasmic pockets of degenerated materials and focal cytoplasmic degradation) also occurred in later time points (16-24 weeks). Such mitochondrial changes were not identical with those induced by pure cadmium. Taken together, we suggest that mitochondria appeared to be the target of QD705 toxicity and specific mitochondrial markers may be useful parameters for toxicity assessments of QDs or other metal-based nanomaterials.

Cd/Se/Te-based quantum dot 705 modulated redox homeostasis with hepatotoxicity in mice.

The objective of this study was to investigate whether quantum dot 705 (QD705) disrupts the cellular antioxidant systems leading to hepatotoxicity in mice. Mice were intravenously injected with QD705 and then sacrificed at week 12 or 16. Homeostasis of antioxidant-related metals, antioxidant activities, induction of oxidative stress, and toxicity in the liver were investigated. Although no histopathological change was observed, a time- and dose-dependent increase in metallothionein expression and reduction in liver function was noticed. Increased copper, zinc, and selenium levels and enhancements of the trace metal-corresponding transporters were noted at week 12. At week 16, a decline of selenium from its elevated level at week 12 was observed, which was accompanied by changes in glutathione peroxidase activity as well as in redox status. A significant reduction in superoxide dismutase activity was observed at 16 weeks. Furthermore, a corresponding elevation of heme oxygenase-1 expression, 8-oxo-7,8-dihydro-2'-deoxyguanosine, interleukin-6 and tumor necrosis factor-alpha suggested the presence of oxidative stress, oxidative DNA damage and inflammation.

Effects of gallium on immune stimulation and apoptosis induction in human peripheral blood mononuclear cells.

Gallium is commonly used in the semiconductor industry and medical field. Biologically, gallium is able to interrupt iron metabolism. Exposure to gallium has been shown to affect the human immune system. The purpose of this study was to investigate the in vitro biological effects of different gallium concentrations on cultured human peripheral blood mononuclear cells (PBMCs) in terms of cell growth, cytokine release, and apoptosis induction. In addition, the in vivo effects of gallium were analyzed by Wistar rat model. Our results revealed that low concentrations (1-10 microg/ml) of gallium promoted cells to enter the S phase of cell cycle and enhanced cellular release of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, both in vitro and in vivo. In contrast, high concentrations of gallium (50-100 microg/ml) induced apoptosis. Furthermore, gallium-induced cytokine release and apoptosis could be inhibited by iron-saturated transferrin (Tf-Fe). These results suggest that the concentration-dependent effects of gallium on PBMCs are related to iron metabolism.