Abstract
Abstract Arsenic (As) is a semi-metal which causes health problems in human, and immune system has been documented as one of the main target of arsenic toxicity. Apoptosis has a crucial role in regulation of immune system, but it can also have an important role in As immune suppression. So, we decided to assess the comprehensive mechanism of As cytotoxic effect on lymphocytes isolated from human blood. We determine the direct effect of arsenic on human lymphocytes which have a key role in immune system functionality. To evaluate the mechanism of arsenic toxicity on human lymphocytes, we use accelerated cytotoxicity mechanisms screening (ACMS) technique. Lymphocytes were isolated from blood of healthy persons using Ficoll-paque PLUS standard method. Following treatment of human lymphocytes with 0.05-50 μM of arsenic for 12 h, cell viability was measured. For determination of mechanistic parameters, isolated human lymphocytes incubated with 1/2IC5012h (7.5 μM), IC5012h (15 μM) and 2IC5012h (30 μM) for 2, 4 and 6 h. The results of this study demonstrate arsenic-associated apoptosis in human lymphocytes is mainly through enhancement of intracellular calcium which causes oxidative stress and following adverse effect on lymphocytes organelles (like mitochondria and lysosome). Involvement of cellular proteolysis, activation of caspase-3, lipid peroxidation and stimulation of cytokines (IL2, INF-gamma and TNF-alpha) production were also associated with arsenic induced lymphocyte toxicity.
Highlights
The results show arsenic-associated apoptosis in human lymphocytes is mainly through enhancement of intracellular calcium, oxidative stress, cytokine production and following adverse effect on lymphocytes
Subchronic exposure to As2O3 causes oxidative stress, inflammation and heat shock response in the brain (Zhao et al, 2017), liver (Zhang et al, 2016b) and immune organs (Guo et al, 2016). In this investigation we have showed that arsenic, at an environmentally achievable concentration, causes apoptosis in normal peripheral blood lymphocytes through mitochondrial pathway via raising oxidative stress and by regulating cytokines
Results of this study show that arsenic decrease viability of isolated human lymphocytes via oxidative stress induction, which in turn cause following cell organelles and macromolecules damage
Summary
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