Acute cadmium exposure enhances AP-1 DNA binding and induces cytokines expression and heat shock protein 70 in HepG2 cells

Souza, Verónica; Escobar, Ma. del Carmen; Gómez-Quiroz, Luís Enrique; Bucio, Leticia; Hernández, Elizabeth; Cossio, Edmundo Chávez; Gutiérrez-Ruı́z, Ma.Concepción

doi:10.1016/j.tox.2004.01.006

Cited by 83 publications

(48 citation statements)

References 47 publications

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“…Particular attention has been paid to the role of tumor necrosis factor α (TNF-α) in Cd hepatotoxicity [28]. It has been shown that anti-TNF-α antibodies prevented Cd-induced secretion of acute phase proteins and gene expression of interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-8 (IL-8) in human hepatoma cell line HepG2 [29]. In addition, increased expression of IL-1β, TNF-α, IL-6 and IL-8 have been demonstrated in hepatocyte [30] or HepG2 cells exposed to Cd [29].…”

Section: Involvement Of Inflammatory Mediators and Adhesion Moleculesmentioning

confidence: 99%

“…It has been shown that anti-TNF-α antibodies prevented Cd-induced secretion of acute phase proteins and gene expression of interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-8 (IL-8) in human hepatoma cell line HepG2 [29]. In addition, increased expression of IL-1β, TNF-α, IL-6 and IL-8 have been demonstrated in hepatocyte [30] or HepG2 cells exposed to Cd [29]. Moreover, TNF-α and IL-1β are recognized to stimulate the production of adhesion molecules, such as intercellular adhesion molecule-1 (IMAC-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin, β 2 -integrin Mac-1 in the liver, that induce the recruitment, adherence and activation of circulating inflammatory cells [31].…”

Section: Involvement Of Inflammatory Mediators and Adhesion Moleculesmentioning

confidence: 99%

“…The final step is transmigration, which is mediated by platelet-endothelial adhesion molecule-1 (PECAM-1) suggesting an important role for these adhesion molecules during Cd hepatoxicity [31]. In addition, ROS promote inflammation by enhancing the activation of the transcription factors, such as nuclear factor-κB (NF-κB) and the activator protein-1 (AP-1), which provide signals for the expression of proinflammatory and adhesion molecules genes [34,29]. This idea is supported by fact that N-acetyl cysteine (NAC), a GSH precursor, could inhibit cadmium-induced AP-1 activation.…”

Section: Involvement Of Inflammatory Mediators and Adhesion Moleculesmentioning

confidence: 99%

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Liver and Cadmium Toxicity

2013

J Drug Metab Toxicol

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Section: Involvement Of Inflammatory Mediators and Adhesion Moleculesmentioning

confidence: 99%

Section: Involvement Of Inflammatory Mediators and Adhesion Moleculesmentioning

confidence: 99%

Section: Involvement Of Inflammatory Mediators and Adhesion Moleculesmentioning

confidence: 99%

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Liver and Cadmium Toxicity

2013

J Drug Metab Toxicol

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“…Pretreating HepG2 cells with 100 mg/ml of NAC has been shown to reverse cytotoxicity induced by cadmium exposure. 34 …”

Section: Nac Pretreatmentmentioning

confidence: 99%

In vitro effect of N-acetylcysteine on hepatocyte injury caused by dichlorodiphenyltrichloroethane and its metabolites

et al. 2013

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The organochlorine pesticide, dichlorodiphenyltrichloroethane (DDT), is still used to combat the spread of malaria in several developing countries despite its accumulation and known hepatotoxic effects that have been demonstrated both in vitro and in vivo. N-Acetylcysteine (NAC) is a recognized hepatoprotective agent that has been reported to reduce hepatotoxicity initiated by many different compounds. The aim of this study was to determine whether NAC could counter in vitro hepatocyte injury induced by DDT or its two major metabolites, dichlorodiphenyldichloroethylene and dichlorodiphenyldichloroethane. HepG2 cell cultures were used to assess the following parameters of toxicity: cellular viability, intracellular levels of reactive oxygen species (ROS), mitochondrial membrane potential and initiation of apoptosis. None of the three test compounds induced ROS generation, yet exposure to any of the three compounds produced mitochondrial hyperpolarization, which was countered by NAC pretreatment. All three test compounds also induced apoptotic cell death, which was inhibited by NAC. Despite NAC counteracting some adverse intracellular changes due to organochlorine exposure, it appeared to aggravate the cytotoxic effects of the organochlorine compounds at low test concentrations. As the same outcome may also occur in vivo, results from the present study raise concern about the use of NAC as treatment for DDT-induced hepatotoxicity.

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“…Following internalization, the bound protein is digested in the lysosome with the release of free ionic cadmium. In an in vitro experiment, the free ionic form of cadmium (CdCl 2 ) induced expression of cytokines (TNF-α and IL-1β) in HepG2 cells (Souza et al 2004). These inductive effects of free cadmium on proand inflammatory cytokines remain to be substantiated with in vivo experiments because the vast majority of cadmium in blood circulation is protein bound with extremely low concentrations of unbound form.…”

Section: Liver Inflammationmentioning

confidence: 99%

Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

Satarug

2012

Tohoku J. Exp. Med.

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Many decades after an outbreak of severe cadmium poisoning, known as Itai-itai disease, cadmium continues to pose a significant threat to human health worldwide. This review provides an update on the effects of this environmental toxicant cadmium, observed in numerous populations despite modest exposure levels. In addition, it describes the current knowledge on the link between heme catabolism and glycolysis. It examines novel functions of heme oxygenase-2 (HO-2) that protect against type 2-diabetes and obesity, which have emerged from diabetic/obese phenotypes of the HO-2 knockout mouse model. Increased cancer susceptibility in type-2 diabetes has been noted in several large cohorts. This is a cause for concern, given the high prevalence of type-2 diabetes worldwide. A lifetime exposure to cadmium is associated with pre-diabetes, diabetes, and overall cancer mortality with sex-related differences in specific types of cancer. Liver and kidney are target organs for the toxic effects of cadmium. These two organs are central to the maintenance of blood glucose levels. Further, inhibition of gluconeogenesis is a known effect of heme, while cadmium has the propensity to alter heme catabolism. This raises the possibility that cadmium may mimic certain HO-2 deficiency conditions, resulting in diabetic symptoms. Intriguingly, evidence has emerged from a recent study to suggest the potential interaction and co-regulation of HO-2 with the key regulator of glycolysis: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4). HO-2 could thus be critical to a metabolic switch to cancer-prone cells because the enzyme PFKFB and glycolysis are metabolic requirements for cell proliferation and resistance to apoptosis.

show abstract

Acute cadmium exposure enhances AP-1 DNA binding and induces cytokines expression and heat shock protein 70 in HepG2 cells

Cited by 83 publications

References 47 publications

Liver and Cadmium Toxicity

Liver and Cadmium Toxicity

In vitro effect of N-acetylcysteine on hepatocyte injury caused by dichlorodiphenyltrichloroethane and its metabolites

Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

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