PMID- 28774209 OWN - NLM STAT- MEDLINE DCOM- 20180814 LR - 20180814 IS - 1537-6524 (Electronic) IS - 1537-6516 (Linking) VI - 28 IP - 2 DP - 2018 Feb TI - Analysis of cytotoxic effects of nickel on human blood lymphocytes. PG - 79-86 LID - 10.1080/15376516.2017.1364314 [doi] AB - 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 NiCl(2) 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 NiCl(2) for 12 h. Determination of mechanistic parameters was performed 2, 4 and 6 h after treatment of cells with (1/2) EC50(12h), EC50(12h) and 2EC50(12h) of NiCl(2). Our results demonstrate that cytotoxicity of NiCl(2) 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. FAU - Zarei, Mohammad Hadi AU - Zarei MH AD - a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran. FAU - Hosseini Shirazi, Seyed Farshad AU - Hosseini Shirazi SF AD - a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran. FAU - Aghvami, Marjan AU - Aghvami M AD - a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran. FAU - Salimi, Ahmad AU - Salimi A AD - b Department of Pharmacology and Toxicology, School of Pharmacy , Ardabil University of Medical Science , Ardabil , Iran. FAU - Pourahmad, Jalal AU - Pourahmad J AD - a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Shahid Beheshti University of Medical Sciences , Tehran , Iran. LA - eng PT - Journal Article DEP - 20171122 PL - England TA - Toxicol Mech Methods JT - Toxicology mechanisms and methods JID - 101134521 RN - 0 (Reactive Oxygen Species) RN - 696BNE976J (nickel chloride) RN - 7OV03QG267 (Nickel) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - GAN16C9B8O (Glutathione) SB - IM MH - Caspase 3/drug effects/metabolism MH - Cell Survival/drug effects MH - Cells, Cultured MH - Enzyme Activation/drug effects MH - Glutathione/metabolism MH - Healthy Volunteers MH - Humans MH - In Vitro Techniques MH - Lethal Dose 50 MH - Lipid Peroxidation/drug effects MH - Lymphocytes/*drug effects/metabolism MH - Lysosomes/drug effects/metabolism MH - Membrane Potential, Mitochondrial/drug effects MH - Nickel/*toxicity MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - Human lymphocytes OT - cellular proteolysis OT - cytotoxicity OT - nickel EDAT- 2017/08/05 06:00 MHDA- 2018/08/15 06:00 CRDT- 2017/08/05 06:00 PHST- 2017/08/05 06:00 [pubmed] PHST- 2018/08/15 06:00 [medline] PHST- 2017/08/05 06:00 [entrez] AID - 10.1080/15376516.2017.1364314 [doi] PST - ppublish SO - Toxicol Mech Methods. 2018 Feb;28(2):79-86. doi: 10.1080/15376516.2017.1364314. Epub 2017 Nov 22.