Perfluorooctanesulfonate (PFOS) Induces Apoptosis Signaling and Proteolysis in Human Lymphocytes through ROS Mediated Mitochondrial Dysfunction and Lysosomal Membrane Labialization.

Perfluorinated compounds (PFCs) such as perfluorooctanesulfonate (PFOS) are stable chemicals that accumulate in biological matrix. Toxicity of these compounds including immunotoxicity has been demonstrated in experimental models and wildlife. Although limited number of studies examined the effects of PFOS on human lymphocytes but so far no research has investigated the complete mechanisms of PFOS cytotoxicity toward human lymphocytes. The main goal of this investigation was to find out the mechanisms underlying the cytotoxic effect of PFOS toward human lymphocytes using accelerated cytotoxicity mechanisms screening (ACMS) technique. Human lymphocytes were isolated from blood of healthy donors using Ficoll-paquePLUS standard method. Cell viability was determined following 12 h of incubation of human lymphocytes with 100-500 µM PFOS. Our results showed that IC50 concentration (163.5 µM) of PFOS reduced viability of human lymphocytes approximately 50% via increased ROS formation, lipid peroxidation, glutathione depletion and damage to cell sub organelles such as mitochondria and lysosomes. Besides, in this study we demonstrated involvement of cellular proteolysis and activation of caspase-3 in PFOS induced lymphocyte cytotoxicity. We finally concluded that at environmentally related concentration, PFOS can induce toxic effect toward human lymphocytes through induction of oxidative stress and damage to cell sub organelles.

Analysis of cytotoxic effects of nickel on human blood lymphocytes.

Nickel compounds possess many applications in different industrial processes. Human beings are exposed to nickel commonly through occupational exposure and food. Although a few studies so far have investigated the effects of nickel compounds on human lymphocytes, the complete mechanism of cytotoxicity of this metal on human lymphocytes is yet to be determined. The intention of this paper was to determine the cytotoxicity mechanism of water soluble NiCl2 toward human lymphocytes using the accelerated cytotoxicity mechanisms screening (ACMS) technique. Human lymphocytes were isolated from the blood of healthy subjects based on Ficoll-Paque PLUS standard method. For the assessment of cell viability, lymphocytes were incubated with 0.05-1 mM NiCl2 for 12 h. Determination of mechanistic parameters was performed 2, 4 and 6 h after treatment of cells with ½ EC5012h, EC5012h and 2EC5012h of NiCl2. Our results demonstrate that cytotoxicity of NiCl2 on human lymphocytes is associated with increased ROS formation, mitochondrial membrane potential collapse, glutathione depletion, lysosomal membrane damage, cellular proteolysis and activation of caspase-3 before cytotoxicity ensued.

Evaluation of the Effect of PEGylated Single-Walled Carbon Nanotubes on Viability and Proliferation of Jurkat Cells.

Among the numerous nanosized drug delivery systems currently under investigation, carbon nanotubes (CNTs), regardless of being single or multiple-walled, offer several advantages and are considered as promising candidates for drug targeting. Despite the valuable potentials of CNTs in drug delivery, their toxicity still remains an important issue. After the PEGylation of single-walled CNTs (SWCNTs) with phospholipid-PEG (Pl-PEG) conjugates to prepare water-dispersible nanostructures, the present study was designed to evaluate whether the functionalization with Pl-PEG derivatives could alter the cytotoxic response of cells in culture, affect their viability and proliferation. In-vitro cytotoxicity screens were performed on cultured Jurkat cells. The SWCNTs samples used in this exposure were pristine SWCNTs, Pl-PEG 2000/5000-SWCNTs at various concentrations. Jurkat cells were first incubated for 3 h at 37°C with test materials and seeded in 6-well culture plates at a given concentration. The plates were then incubated for 24, 48 and 72 h at 37°C in a 5% CO2 humidified incubator. Cell Viability and proliferation assay were performed using trypan blue exclusion test and the cell cycle kinetic status of Jurkat cells was analyzed by flow cytometry. Cell morphology was finally studied using double staining technique and a fluorescence microscope. We found that, regardless of the duration of exposure, functionalized SWCNTs were substantially less toxic, compared to pure SWCNTs and that the molecular weight of Pl-PEGs played an important role at higher concentrations. In conclusion, our noncovalent protocol seemed to be effective for increasing SWCNTs biocompatibility.