Effect of dibutyltin on ATP levels in human natural killer cells

Dudimah, Fred Duafalia; Gibson, Constance; Whalen, Margaret M.

doi:10.1002/tox.20252

Cited by 28 publications

(47 citation statements)

References 32 publications

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“…It is known that DBTCl induces cytotoxicity (apoptosis and/ or necrosis) and has anti-proliferative activity in some in vitro studies (Boyer, 1989;Hoth et al, 2005;Ferreira et al, 2013). It is also reported that the cytotoxicity is attributed to the inhibition of α-ketoacid oxidation, resulting from a decrease in intercellular ATP levels and the inhibition of mitochondrial respiration (Dudimah et al, 2007;Ueno et al, 2003). On the other hand, the LA-ICP-MS analysis is a very useful method for the investigation of elemental distributions in paraffin sections and is becoming one of the important tools for pathology (Yamagishi et al, 2016;Egger et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Effect of dibutyltin on placental and fetal toxicity in rat

et al. 2017

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-In order to elucidate the effect of chorioallantoic and yolk sac placenta on the embryonic/fetal toxicity in dibutyltin dichloride (DBTCl)-exposed rats, we examined the histopathological changes and the tissue distribution of dibutyltin in the placentas and embryos. DBTCl was orally administered to the groups at doses of 0 mg/kg during gestation days (GD)s 7-9 (control group) and 20 mg/kg during GDs 7-9 (GD7-9 treated group), and GDs 10-12 (GD10-12 treated group). The total fetal mortality was increased, and malformations characterized by craniofacial dysmorphism were detected in the GD7-9 treated group. The embryonic/fetal weight and placental weight showed a decrease in both DBTCl-treated groups. Histologically, some embryos on GD 9.5 in the GD7-9 treated group underwent apoptosis without any changes of yolk sac. In the laser ablation-inductively coupled plasma-mass spectrometry analysis (LA-ICP-MS), tin was detected in the embryo, allantois, yolk sac, ectoplacental cone and decidual mass surrounding the conceptus on GD 9.5 in the GD7-9 treated group. Thus, it is considered that the embryo in this period is specifically sensitive to DBTCl-induced apoptosis, compared with other parts. The chorioallantoic placentas in both DBTCl-treated groups showed the developmental delay and hypoplasia in the fetal parts of placenta, resulting from apoptosis and mitotic inhibition. Thus, it was speculated that the DBTCl-induced malformations and fetal resorption resulted from the apoptosis in the embryo caused by the direct effect of DBTCl. The DBTCl-induced lesions in the chorioallantoic placenta were a non-specific transient developmental retardation in the fetal parts of placenta, leading to intrauterine growth retardation.

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Section: Discussionmentioning

confidence: 99%

Effect of dibutyltin on placental and fetal toxicity in rat

et al. 2017

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“…This inhibition of NK lytic function may be due to their ability to induce activation/phosphorylation of MAPKs and MAP2Ks (Cato et al, 2014). Other environmental contaminants such as tributyltin (TBT) and dibutyltin (DBT) (Kimbrough, 1976) that decrease NK lytic function (Dudimah et al, 2007a,b), while activating the MAPK pathway (Aluoch et al, 2006; Odman- Ghazi et al, 2010), have been shown to alter IFNγ secretion from human immune cells (Lawrence et al, 2015). Thus, it is crucial to determine whether HBCD and TBBPA are also able to alter the secretion of IFNγ from human immune cells.…”

Section: Discussionmentioning

confidence: 99%

Hexabromocyclododecane and tetrabromobisphenol A alter secretion of interferon gamma (IFN-γ) from human immune cells

Almughamsi

Whalen

2015

Arch Toxicol

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Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are brominated flame retardant compounds used in a variety of applications including insulation, upholstery, and epoxy resin circuit boards. Interferon gamma (IFNγ) is an inflammatory cytokine produced by activated T and NK cells that regulates immune responsiveness. HBCD and TBBPA are found in human blood and previous studies have shown that they alter the ability of human natural killer (NK) lymphocytes to destroy tumor cells. This study examines whether HBCD and TBBPA affect the secretion of IFNγ from increasingly complex preparations of human immune cells; purified NK cells, monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCs), and PBMCs. Both HBCD and TBBPA were tested at concentrations ranging from 0.05–5 μM. HBCD generally caused increases in IFNγ secretion after 24 h, 48 h, and 6 day exposures in each of the different cell preparations. The specific concentration of HBCD that caused increases as well as the magnitude of the increase varied from donor to donor. In contrast, TBBPA tended to decrease secretion of IFNγ from NK cells, MD-PBMCs and PBMCs. Thus, exposure to these compounds may potentially disrupt the immune regulation mediated by IFNγ. Signaling pathways that have the capacity to regulate IFNγ production (nuclear factor kappa B (NFκB), p44/42, p38, JNK) were examined for their role in the HBCD-induced increases in IFNγ. Results showed that the p44/42 (ERK1/2) MAPK pathway appears to be important in HBCD-induced increases in IFNγ secretion from human immune cells.

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“…It decreases the ability of human NK cells to destroy tumor cells with accompanying decreases in cytotoxic and cell surface protein expression (Dudimah et al, 2007; Catlin et al ., 2005; Whalen et al, 2002). In addition, DBT alters the secretion of tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) from human lymphocytes (Hurt et al, 2013; Lawrence et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Dibutyltin‐induced alterations of interleukin 1beta secretion from human immune cells

Brown

Tehrani

Whalen

2016

J of Applied Toxicology

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Dibutyltin (DBT) is used to stabilize polyvinyl chloride (PVC) plastics (including pipes that distribute drinking water) and as a de-worming agent in poultry. DBT is found in human blood, and DBT exposures alter the secretion of tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) from lymphocytes. Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine that regulates cellular growth, tissue restoration, and immune response regulation. IL-1β plays a role in increasing invasiveness of certain tumors. This study reveals that exposures to DBT (24 h, 48 h, and 6 day) modify the secretion of IL-1β from increasingly reconstituted preparations of human immune cells (highly enriched human natural killer (NK) cells, monocyte-depleted (MD) peripheral blood mononuclear cells (MD-PBMCs), PBMCs, granulocytes, and a preparation combining both PBMCs and granulocytes (PBMCs+granulocytes)). DBT altered IL-1β secretion from all cell preparations. Higher concentrations of DBT (5 and 2.5 μM) decreased the secretion of IL-1β, while lower concentrations of DBT (0.1 and 0.05 μM) increased the secretion of IL-1β. Selected signaling pathways were examined in MD-PBMCs to determine if they play a role in DBT-induced elevations of IL-1β secretion. Pathways examined were IL-1β converting enzyme (Caspase-1), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa B (NFκB). Caspase 1 and MAPK pathways appear to be utilized by DBT in increasing IL-1β secretion. These results indicate that DBT alters IL-1β secretion from human immune cells in an ex vivo system utilizing several IL-1β regulating signaling pathways. Thus, DBT may have the potential to alter IL-1β secretion in an in vivo system.

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Effect of dibutyltin on ATP levels in human natural killer cells

Cited by 28 publications

References 32 publications

Effect of dibutyltin on placental and fetal toxicity in rat

Effect of dibutyltin on placental and fetal toxicity in rat

Hexabromocyclododecane and tetrabromobisphenol A alter secretion of interferon gamma (IFN-γ) from human immune cells

Dibutyltin‐induced alterations of interleukin 1beta secretion from human immune cells

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