Copper-induced immunotoxicity involves cell cycle arrest and cell death in the spleen and thymus

Mitra, Sangeeta; Keswani, Tarun; Dey, Manali; Bhattacharya, Shashwati; Sarkar, Samrat; Goswami, Suranjana; Ghosh, Nabanita; Dutta, Anuradha; Bhattacharyya, Arindam

doi:10.1016/j.tox.2011.12.013

Cited by 55 publications

(37 citation statements)

References 31 publications

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“…Induction of apoptosis has been reported to be the significant mechanism of copper-and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced thymus damage (Kamath et al, 1997;Mitra et al, 2012). In the present study, we also provide one possible mechanism, i.e., an induction of apoptosis, to explain ANE-mediated inhibition of thymocyte proliferation and IL-2 production.…”

Section: Discussionmentioning

confidence: 54%

Impairment of thymocyte function via induction of apoptosis by areca nut extract

Lee

Lin

Liu

et al. 2013

Journal of Immunotoxicology

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Areca quid (AQ) chewing is a popular oral habit, especially in Southeast Asia cultures, in which children may be engaged in the addictive habit early in their lives. Extracts of areca nuts, the main component of AQ, have been shown to affect the functionality of T-cells. However, the potential influence of ANE on the development of T-cells is unknown. This study, therefore, investigated the impact of areca nut extracts (ANE) on thymocytes and the potential mechanisms of action. Mice administered intraperitoneally with ANE at 1, 5, or 25 mg/kg daily for 5 days showed significant dose-dependent reductions in thymocyte viability. A marked decrease in the total number of thymocytes and the proportion of thymic CD4 þ CD8þ cells was observed in the 25 mg ANE/kg-treated mice, whereas the proportion of CD4 and CD8 single positive and CD4À CD8 À cells was significantly increased. Further examination on the functionality of thymocytes showed that ANE suppress IL-2 production both ex vivo and in vitro. These results suggest that ANE may attenuate the development and functionality of thymic T-cells. ANE also directly induced apoptosis in thymic T-cells through activation of casapase-3 and apoptosis inducing factor (AIF). Collectively, the data suggested that the thymus is a sensitive target to ANE. Early exposure to ANE may interfere with the development and functionality of thymic T-cells.

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Section: Discussionmentioning

confidence: 54%

Impairment of thymocyte function via induction of apoptosis by areca nut extract

Lee

Lin

Liu

et al. 2013

Journal of Immunotoxicology

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“…Among these proteins, there is the EndoG, a mitochondrion-specific nuclease that translocates to the nucleus during cell cycle arrest and apoptosis. Once released from mitochondria, EndoG cleaves chromatin DNA into nucleosomal fragments (independently of caspases); thus, EndoG represents a novel caspase independent apoptotic pathway (Huang et al, 2006;Mitra et al, 2012). The exposure of organisms to xenobiotics such as heavy metals creates a stress condition that might interfere with the maintenance of homeostasis.…”

Section: Discussionmentioning

confidence: 99%

In vitro effect of cadmium and copper on separated blood leukocytes of Dicentrarchus labrax

Vazzana¹,

Celi²,

Tramati³

et al. 2014

Ecotoxicology and Environmental Safety

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a b s t r a c tThe immunotoxic effects of heavy metals on blood leukocytes of sea bass (Dicentrarchus labrax) were examined. The cells, separated by a discontinuous Percoll-gradients, were exposed in vitro to various sublethal concentrations of cadmium and copper (10 À 7 M, 10 À 5 M, and 10 À 3 M) and their immunotoxic effect was then evaluated by measuring neutral red uptake, MTT assay, DNA fragmentation and Hsp70 gene expression. First of all, we demonstrated that the cells treated in vitro could incorporate Cd and Cu. A relationship between heavy metal exposure and dose-time-dependent alterations in responses of leukocytes from blood was found for both metals, but copper was more immunotoxic than cadmium in all assays performed. A significant reduction in the cells' ability to uptake neutral red and viability by MTT assay was recorded, indicating that both cadmium and copper could change the membrane permeability, inducing cellular apoptosis when the concentration of metals reached 10 À 3 M. The apoptotic effect may also explain the high level of cytotoxicity found when the leukocytes were exposed to higher concentration of metals. These results demonstrated that toxic effect of copper and cadmium affect on the mechanisms of cellmediated immunity reducing the immune defences of the organism.

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“…The Cu is an essential trace element for human physiological processes; however, overexposure of this metal exerts potential adverse health impacts/immunotoxicological effects [11]. Studies on the presence of Cu in human seminal plasma provide evidence for inverse relationships between human semen quality and Cu concentration.…”

Section: Discussionmentioning

confidence: 99%

“…The Cu is also immunotoxic as Cu treated mice evidence immunotoxicity as indicated by dose-related decreases and increases, respectively, in thymic and splenic weights. Histomorphological changes evidenced in these organs are thymic atrophy, white pulp shrinkage in the spleen, and apoptosis of splenocytes and thymocytes [11]. The male patient under consideration had long Cu exposure before developing MS.…”

Section: Discussionmentioning

confidence: 99%

Healthy birth after use of sperm from a male who suffered from copper toxicity

Javed¹,

Michael²

2014

Cureus

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Copper-induced immunotoxicity involves cell cycle arrest and cell death in the spleen and thymus

Cited by 55 publications

References 31 publications

Impairment of thymocyte function via induction of apoptosis by areca nut extract

Impairment of thymocyte function via induction of apoptosis by areca nut extract

In vitro effect of cadmium and copper on separated blood leukocytes of Dicentrarchus labrax

Healthy birth after use of sperm from a male who suffered from copper toxicity

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