Tellurium tetrachloride and diphenyl ditelluride cause cytotoxicity in rat hippocampal astrocytes

• Published in: Food and chemical toxicology 2011-10, Vol.49 (10), p.2564-2574
• Main Authors: Roy, Shalini, Hardej, Diane
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Benzene Derivatives - toxicity; Biological and medical sciences; biphenyl; caspases; Caspases - analysis; Cell Survival - drug effects; cytochrome c; Cytochromes c - analysis; Cytotoxicity; Diphenyl ditelluride; Formazans - chemistry; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; lethal concentration 50; Medical sciences; microscopy; Microscopy, Electron, Scanning; Organometallic Compounds - toxicity; Rat hippocampal astrocytes; Rats; Rats, Sprague-Dawley; spectroscopy; Tellurium; Tellurium - toxicity; Tellurium tetrachloride; tetrazolium; Tetrazolium Salts - chemistry; Thiobarbituric Acid Reactive Substances - analysis; thiobarbituric acid-reactive substances; Toxicology; viability
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2011.06.072

► Te tetrachloride and diphenyl ditelluride were assessed for toxicity in astrocytes. ► Cell death varied for the compounds despite similar LD50 (apoptosis vs. necrosis). ► Lipid peroxidation was not observed in either compound via TBARS assay. ► Exposure to compounds resulted in TE accumulation (Atomic Absorption Spectroscopy). ► In vitro system is useful to determine mechanisms of cell death in Te exposed cells. Tellurium tetrachloride (TeCl4) and diphenyl ditelluride (DPDT) cytotoxicity, was investigated in rat astrocytes. Concentrations of 0.24–250μM (24h) were tested for viability using MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and trypan blue exclusion. MTT showed significant decreases at all concentrations tested for both compounds. Significant decreases in viability were seen in 1.95–250μM of DPDT and 0.97–250μM of TeCl4 with trypan blue exclusion. The LC50 for both compounds was 62.5μM. Light and scanning microscopy confirm toxicity observed at higher concentrations. Thiobarbituric acid reactive substances (TBARs) assay, TUNEL, cytochrome c and caspase release were carried out. No significant increase in TBARS with either agent was observed (15.625–62.5μM). TUNEL and cytochrome c assays demonstrated apoptosis in TeCl4 treated cells (31.25–125μM). Non-apoptotic cells were observed in DPDT treated cells. Studies of caspase 3/7 and caspase 9 indicated increased activity in TeCl4 but not in DPDT treated cells. Optical Emission Spectroscopy of DPDT and TeCl4 treated cells demonstrated significant accumulation of elemental tellurium in all treatment groups (31.25–125μM). We conclude that DPDT and TeCl4 are cytotoxic to astrocytes. TeCl4 treated cells die via the intrinsic apoptotic pathway. Accumulation of tellurium occurs with both compounds, but results in different mechanisms of cell death.