Analysis of cytotoxic effects of nickel on human blood lymphocytes

Abstract

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 EC50_12h, EC50_12h and 2EC50_12h 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.

Keywords:

• Human lymphocytes
• nickel
• cellular proteolysis
• cytotoxicity

Acknowledgements

The results presented in this article were partly extracted from the thesis of Dr. Mohammad Hadi Zarei (Ph.D. graduate of Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences) who performed his theses under the supervision of Prof. Dr. Jalal Pourahmad and Prof. Dr. Seyed Farshad Hosseini Shirazi. The investigation was performed in Prof. Jalal Pourahmad's laboratory in the Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Disclosure statement

The authors declare that there is no conflict of interest. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.