scholarly journals Toxicity of arsenic on isolated human lymphocytes: The key role of cytokines and intracellular calcium enhancement in arsenic-induced cell death

2019 ◽  
Vol 42 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Mohammad Hadi Zarei ◽  
Jalal Pourahmad ◽  
Ehsan Nassireslami
Keyword(s):  
Immune System ◽  
Intracellular Calcium ◽  
Caspase 3 ◽  
Human Lymphocytes ◽  
Tnf Alpha ◽  
Arsenic Toxicity ◽  
Alpha Production ◽  
Isolated Human Lymphocytes

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.

Ascorbic acid improves mitochondrial function in liver of arsenic-treated rat

2010 ◽  
Vol 26 (5) ◽  
pp. 265-272 ◽  
Author(s):  
Sohini Singh ◽  
Suresh Vir Singh Rana
Keyword(s):  
Reactive Oxygen Species ◽  
Ascorbic Acid ◽  
Mitochondrial Function ◽  
Caspase 3 ◽  
Succinic Dehydrogenase ◽  
Reactive Oxygen ◽  
Ultrastructural Changes ◽  
Arsenic Toxicity ◽  
Oxygen Species

Arsenic is an ubiquitous and well-documented carcinogenic metalloid. The most common source of arsenic is drinking water. The mechanism of arsenic toxicity in a cell has historically been centered around its inhibitory effects on cellular respiration and mitochondrial injury. Ascorbic acid, a low molecular weight, water-soluble antioxidant, improves the reduced glutathione (GSH) status by recycling oxidized glutathione. Ascorbic acid can improve mitochondrial function by improving the thiol status; thereby preventing reactive oxygen species— mediated damage to liver as well as kidney. Ascorbic acid has been shown to protect membrane and other cellular compartments by regenerating vitamin E. Therefore, ascorbic acid seems to be a suitable protective factor against arsenic toxicity. Present reports describe the effect of ascorbic acid on oxidative phosphorylation, adenosine triphosphatase (ATPase), succinic dehydrogenase, caspase-3 and apoptosis in the liver of rats treated with arsenic trioxide (AsIII). Ultrastructural changes in the mitochondria have also been reported. We show that cotreatments with ascorbic acid and AsIII improve mitochondrial structure and function. We attribute these improvements mainly to antioxidative role of ascorbic acid. Apoptosis was restricted due to caspase-3 inhibition. Ascorbic acid could protect DNA from the attack of reactive oxygen species generated by AsIII. Consequently its events led to improved ADP:O ratio, normalized ATPase activity and restored the activity of succinic dehydrogenase. Overall, results support the protective role of ascorbic acid against As III-induced liver injury.

Upregulation of TNF-alpha production signaling pathways in monocytes from patients with advanced cirrhosis: Possible role of Akt and IRAK-M

2006 ◽  
Vol 45 (2) ◽  
pp. 280-289 ◽  
Author(s):  
Khalid A. Tazi ◽  
Jean-Jacques Quioc ◽  
Véronique Saada ◽  
Annie Bezeaud ◽  
Didier Lebrec ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Tnf Alpha ◽  
Alpha Production ◽  
Advanced Cirrhosis

Physiological and cytokine responses in IL-1 beta-deficient mice after zymosan-induced inflammation

1997 ◽  
Vol 273 (1) ◽  
pp. R400-R406 ◽  
Author(s):  
G. Fantuzzi ◽  
S. Sacco ◽  
P. Ghezzi ◽  
C. A. Dinarello
Keyword(s):  
Lavage Fluid ◽  
Inhibitory Effect ◽  
Tnf Alpha ◽  
Wild Type ◽  
Cytokine Responses ◽  
Alpha Production ◽  
Fluid Levels ◽  
Deficient Mice ◽  
Necrosis Factor

Interleukin (IL)-1 beta-deficient (IL-1 beta -/-) mice exhibited decreased zymosan-induced lethality and reduced production of IL-6 compared with wild-type controls (IL-1 beta +/+). In addition, IL-1 beta -/- mice had a diminished cellular infiltrate (33%) in the peritoneal cavity after zymosan. However, anorexia and hypoglycemia were not affected by the lack of IL-1 beta. The induction of corticosterone was only slightly reduced (14%) in IL-1 beta -/- mice. Peritoneal lavage fluid levels for IL-1 alpha, but not for tumor necrosis factor (TNF)-alpha, were also decreased. To evaluate the role of residual IL-1 alpha production in IL-1 beta -/- mice, we used IL-1-receptor antagonist (IL-1ra). In IL-1 beta +/+ mice, IL-1ra inhibited production of IL-6 after zymosan, without affecting TNF-alpha synthesis. There was no further inhibitory effect of IL-1ra on IL-6 production in IL-1 beta -/- mice, suggesting no role for IL-1 alpha in zymosan-induced IL-6. Our results demonstrate that IL-1 beta plays a significant, although not exclusive, role in the physiological and cytokine responses to zymosan-mediated inflammation.

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