PCB congeners induced mitochondrial dysfunction in Vero cells

Shen, Ke; Shen, Chaofeng; Yu, Jie; Yu, Chunna; Chen, Lei; Shi, Dezhi; Chen, Yingxu

doi:10.1016/j.jhazmat.2010.08.061

Cited by 21 publications

(14 citation statements)

References 38 publications

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“…In addition to their physical, chemical and bio-accumulative characteristics, the ability of PBDEs to spread throughout the environment and accumulate in human beings tissues in a way similar to polychlorinated compounds (PCBs) [1] has made their presence in the environment increasingly disturbing in recent years. It has been shown in the literature that the toxicity of PBDEs depends on the amount of bromine substituent in their structure and is also related to the presence of bromine atoms at the ortho and meta positions [35], as also observed in PCBs [36]. Considering that both BDE-99 and BDE-100, two of the most common congeners found in the environment have 5 bromines connected to their structure, it is to be expected that the structural similarity implies in a similarity between their toxic effects.…”

Section: Discussionmentioning

confidence: 89%

“…It has been shown in the literature that the toxicity of PBDEs depends on the amount of bromine substituent in their structure and is also related to the presence of bromine atoms at the ortho and meta positions , as also observed in PCBs . Considering that both BDE‐99 and BDE‐100, two of the most common congeners found in the environment have 5 bromines connected to their structure, it is to be expected that the structural similarity implies in a similarity between their toxic effects.…”

Section: Discussionmentioning

confidence: 95%

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Polybrominated Diphenyl Ether Congener (BDE‐100) Induces Mitochondrial Impairment

Pereira

Souza

Dorta

2013

Basic Clin Pharma Tox

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Brominated flame retardants are used in various consumer products to increase their resistance to fire and/or high temperatures. Polybrominated diphenyl ethers (PBDEs) are representatives of this class and among the most widely used congeners, and BDE-100 is produced on a large scale. There is a lack of toxicological data about these compounds, which has recently become a matter of concern to the scientific community. The mitochondria are recognized as the main energy-producing organelles, as well as playing a vital role in the maintenance of many cell functions. Therefore, mitochondria were used in the present work as an experimental model to evaluate the effects of the BDE-100 congeners at concentrations ranging from 0.1 lM to 50 lM. The results showed that high concentrations of BDE-100 were able to induce mitochondrial alterations. It was observed that the substance had an affinity for the hydrophilic portion of the mitochondrial membrane, as monitored by ANS, inhibiting the glutamate + malate-stimulated mitochondrial respiration and also inducing dissipation of the mitochondrial membrane potential, deregulation of calcium homoeostasis and mitochondrial swelling, the latter being insensitive to cyclosporin A (CsA) but partially inhibited by Ruthenium Red and N-ethyl maleimide. In addition, a significant reduction in mitochondrial ATP content was found, but on the other hand, no oxidative stress was observed after exposure of the mitochondria to BDE-100. These results show the key role of mitochondria in the cytotoxicity induced by BDE-100.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 95%

Polybrominated Diphenyl Ether Congener (BDE‐100) Induces Mitochondrial Impairment

Pereira

Souza

Dorta

2013

Basic Clin Pharma Tox

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“…Mercury inhibits thioredoxin reductase, which is a key anti-oxidant in cells, while PCBs activate Cyp1a and damage mitochondria, thereby directly contributing to reactive oxygen species formation (Branco et al 2012a; Branco et al 2012b; Shen et al 2011; Yamazaki et al 2011). By affecting both reactive oxygen species formation and inhibiting anti-oxidant defenses, mercury and PCBs may have synergistic effects in terms of observed hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Multiple classes of environmental chemicals are associated with liver disease: NHANES 2003–2004

Christensen

Carrico

Sanyal

et al. 2013

International Journal of Hygiene and Environmental Health

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Biomonitoring studies show that humans carry a body burden of multiple classes of contaminants which are not often studied together. Many of these chemicals may be hepatotoxic. We used the 2003–2004 National Health and Nutrition Examination Survey to evaluate the relationship between alanine aminotransferase (ALT) and 37 environmental contaminants, comprising heavy metals, non-dioxin-like polychlorinated biphenyls (PCBs), and dioxin-like compounds, using a novel method. Linear regression models were constructed for each chemical separately, then as a class, using quartiles to represent exposure and adjusting for age, sex, race, income, and BMI. We then used an optimization approach to compile a weighted sum of the quartile scores, both within and across chemical classes. Using the optimization approach to construct weighted quartile scores, the dioxin like PCB, the non-dioxin like PCB and metal class-level scores were significantly associated with elevated ALT. A significant interaction was detected between the class-level score for metals, and the score for non-dioxin-like PCBs. When including all chemicals in one model, 3 chemicals accounted for 78 % of the weight (Mercury, PCB 180, 3,3’,4,4’,5-PNCB) with the remaining 22% associated with 4 chemicals (a dioxin and 3 PCBs). Validation with a holdout dataset indicated that the weighted quartile sum estimator efficiently identifies reproducible significant associations.

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“…The capacity of these chemicals to induce NAFLD stems from their ability to disrupt mitochondrial function. In vitro and in vivo studies have conclusively shown that toxic metals and certain POPs preferentially accumulate in mitochondria, leading to oxidative damage and disruption of mitochondrial respiration [3], [18], [19]. The result is the accumulation of hepatic lipids due to a loss of mitochondrial function and capacity to engage in β-oxidation.…”

Section: Introductionmentioning

confidence: 99%

Exposure to a Northern Contaminant Mixture (NCM) Alters Hepatic Energy and Lipid Metabolism Exacerbating Hepatic Steatosis in Obese JCR Rats

et al. 2014

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Non-alcoholic fatty liver disease (NAFLD), defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with or without co-exposure to ethanol.

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PCB congeners induced mitochondrial dysfunction in Vero cells

Cited by 21 publications

References 38 publications

Polybrominated Diphenyl Ether Congener (BDE‐100) Induces Mitochondrial Impairment

Polybrominated Diphenyl Ether Congener (BDE‐100) Induces Mitochondrial Impairment

Multiple classes of environmental chemicals are associated with liver disease: NHANES 2003–2004

Exposure to a Northern Contaminant Mixture (NCM) Alters Hepatic Energy and Lipid Metabolism Exacerbating Hepatic Steatosis in Obese JCR Rats

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