tellurium and Necrosis

The toxicity of CdTe QDs with nearly identical maximum emission wavelength but modified with four different ligands (MPA, NAC, GSH and dBSA) to HEK293 and HeLa cells were investigated using flow cytometry, spectroscopic and microscopic methods. The results showed that the cytotoxicity of QDs increased in a dose- and time-dependent manner. No appreciable fraction of cells with sub-G1 DNA content, the loss of membrane integrity, and the swelling of nuclei clearly indicated that CdTe QDs could lead to necrotic cell death in HEK293 cells. JC-1 staining and TEM images confirmed that QDs induced MPT, which resulted in mitochondrial swelling, collapse of the membrane potential. MPT is an important step in QDs-induced necrosis. Moreover, QDs induced MPT through the elevation of ROS. The fluorimetric assay and theoretical analysis demonstrated ROS production has been associated with the internalization of QDs with cells. Due to large surface/volume ratios of QDs, when QDs added in the culture medium, serum proteins in the culture medium will be adsorbed on the surface of QDs. This adsorption of serum protein will change the surface properties and size, and then mediate the cellular uptake of QDs via the clathrin-mediated endocytic pathway. After entering into cells, the translocation of QDs in cells is usually via endosomal or lysosomal vesicles. The rapid degradation of QDs in lysosome and the lysosomal destabilization induce cell necrosis. This study provides a basis for understanding the cytotoxicity mechanism of CdTe QDs, and valuable information for safe use of QDs in the future.

Topics: Cadmium Compounds; Cell Survival; HEK293 Cells; Humans; Ligands; Necrosis; Quantum Dots; Surface Properties; Tellurium

We present a cytological, immunocytochemical, and biochemical study of the cell death of mature myelinating Schwann cells (SCs) in the primary demyelinating neuropathy induced by tellurium (Te). Weaned rats were fed a diet containing 1.1% elemental Te. The animals were killed daily within the first week of Te diet. After 4 to 6 days of Te treatment some SCs underwent degeneration and necrosis. By electron microscopy analysis, degenerating SCs showed chromatin condensation, detachment from the nuclear envelope of condensed chromatin clumps, aggregation of interchromatin granule clusters, formation of intranuclear bundles of microfilaments, and cytoplasmic vesiculation. By confocal laser fluorescence microscopy, chromatin regions were stained with the TUNEL method for in situ labeling of DNA fragmentation and exhibited a progressive reduction of histone signal. In addition, splicing small nuclear ribonucleoprotein (snRNP) factors were redistributed in a few large nuclear domains and bright foci of intranuclear actin were observed. DNA electrophoresis revealed a smear pattern of DNA fragmentation in sciatic nerve samples from Te-treated animals. Upon Te treatment, no degradation of the caspase substrates poly (ADP-ribose) polymerase and lamin B was detected by Western blots or immunocytochemistry, respectively. The peculiar structural rearrangement of the transcription and splicing machinery as well as the vesicular degeneration of the cytoplasm in degenerating SCs support an autophagic cell death of the necrotic type. Unlike the apoptosis of pre-remyelinating SCs (11), this caspase independent cell death of necrotic type involves mature pre-demyelinating SCs and eliminates SCs injured by the neurotoxic effect of Te.

Topics: Actins; Animals; Caspases; Cell Nucleus; Demyelinating Diseases; DNA; DNA Fragmentation; Fluorescent Antibody Technique; In Situ Nick-End Labeling; Male; Necrosis; Rats; Rats, Sprague-Dawley; RNA Splicing; Schwann Cells; Tellurium

Seventy newly hatched ducklings were fed a commercial ration with 500 mg of added Te (as tetrachloride)/kg of feed for up to 28 days. Ducklings were euthanatized at day 14, 21, and 28, the hearts were studied by gross, microscopic, and ultrastructural examination. Cardiac damage was apparent grossly as hydropericardium and myocardial hemorrhage. Histopathologically, the ventricular myocardium had areas of acute hemorrhagic necrosis (often with mineralization), edema, and congestion. Resolving areas of necrosis appeared cellular with macrophages, heterophils, fibroblasts, and pale vacuolated cells with large vesicular nuclei that were identified as dedifferentiated myocytes. Ultrastructurally, necrotic fibers had disrupted contractile material and mineralized mitochondria. In resolving lesions, macrophages were numerous in the interstitium and within necrotic fibers. Also, a population of sublethally injured myocytes was present and appeared as dedifferentiated cardiac muscle cells with few myofibrils, scattered free filaments, prominent sarcoplasmic reticulum, abundant glycogen, and large nuclei with prominent nucleoli. These dedifferentiated myocytes represented a reparative phase of the Te-induced myocardial injury which has been termed "reactive hyperplasia" and "rejuvenating reorganization" in previous models of myocardial damage.

Topics: Animals; Diet; Ducks; Heart; Male; Microscopy, Electron; Myocardium; Necrosis; Organoids; Tellurium