Exposure to Polychlorinated Biphenyls Is Associated With an Increased Risk of Hypertension and Cardiovascular Disease

Hennig

2013

Environ Sci Pollut Res

The nutritional profile of an individual can influence the toxicity of persistent environmental toxicants. Polychlorinated biphenyls (PCBs), prevalent environmental pollutants, are highly lipid soluble toxic compounds that biomagnify through trophic levels and pose cancer, neuro-cognitive, and atherosclerotic risk to human populations. There is a growing body of knowledge that PCBs can initiate inflammatory responses in vivo, and this inflammation can be either exacerbated or ameliorated by nutrition. Data indicate that diets high in certain dietary lipids such as omega-6 fatty acids can worsen PCB-induced vascular toxicity while diets enriched with bioactive food components such as polyphenols and omega-3 polyunsaturated fatty acids can improve the toxicant-induced inflammation. There is evidence that bioactive nutrients protect through multiple cell signaling pathways, but we have shown that lipid raft caveolae and the antioxidant defense controller Nrf2 both play a predominant role in nutritional modulation of PCB-induced vascular toxicity. Interestingly, there appears to be intimate cross-talk between caveolae-related proteins and cellular Nrf2, and focusing on the use of specific bioactive food components that simultaneously alter both pathways may produce a more effective and efficient cytoprotective response to toxicant exposure. The use of nutrition as a protective tool is an economically beneficial means to address the toxicity of persistent environmental toxicants and may become a sensible means to protect human populations from PCB-induced vascular inflammation and associated chronic diseases.

Section: Introductionmentioning

confidence: 99%

Influence of nutrition in PCB-induced vascular inflammation

Hennig

2013

Environ Sci Pollut Res

“…For example, our studies suggest that PCBs, and in particular coplanar PCBs, can increase cellular oxidative stress and induce inflammatory parameters such as inflammatory cytokines, chemokines, and adhesion molecules in the vascular endothelium, which are metabolic events that foster an inflammatory response and atherosclerosis (Eske et al, 2013; Hennig et al, 2002; Lim et al, 2007; Majkova et al, 2009). Through these pro-inflammatory mechanisms, PCBs and related environmental toxicants have been correlated with increased risk of multiple human chronic disease phenotypes including diabetes and heart disease (Carpenter, 2011; Goncharov et al, 2008; Silverstone et al, 2012; Uemura, 2012). Since many populations susceptible to toxicant-induced disease are often also afflicted by diet-induced diseases, future human studies and integrated risk assessments should better investigate the interaction between nutrition and toxicology (Hennig et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Modulation of persistent organic pollutant toxicity through nutritional intervention: Emerging opportunities in biomedicine and environmental remediation

Science of The Total Environment

Dziubla

et al. 2014

Environmental pollution is increasing worldwide, and there is evidence that exposure to halogenated persistent organic pollutants (POPs) such as polychlorinated biphenyls can contribute to the pathology of inflammatory diseases such as atherosclerosis, diabetes, and cancer. Pollutant removal from contaminated sites and subsequent pollutant degradation are critical for reducing the long-term health risks associated with exposure. However, complete remediation of a toxicant from the environment is very difficult and cost-prohibitive. Furthermore, remediation technologies often result in the generation of secondary toxicants. Considering these circumstances, environmentally-friendly and sustainable remediation technologies and biomedical solutions to reduce vulnerability to environmental chemical insults need to be explored to reduce the overall health risks associate with exposure to environmental pollutants. We propose that positive lifestyle changes such as healthful nutrition and consumption of diets rich in fruits and vegetables or bioactive nutrients with antioxidant and/or anti-inflammatory properties will reduce the body’s vulnerability to environmental stressors and thus reduce toxicant-mediated disease pathologies. Interestingly, emerging evidence now implicates the incorporation of bioactive nutrients, such as plant-derived polyphenols, in technologies focused on the capture, sensing and remediation of halogenated POPs. We propose that human nutritional intervention in concert with the use of natural polyphenol sensing and remediation platforms may provide a sensible means to develop primary and long-term prevention strategies of diseases associated with many environmental toxic insults including halogenated POPs.

“…Exposure to persistent environmental pollutants such as polychlorinated biphenyls has been linked to the induction and/or exacerbation of multiple human pathologies including diabetes and atherosclerosis (Gustavsson and Hogstedt, 1997; Goncharov et al, 2008; Goncharov et al, 2010; Carpenter, 2011; Uemura, 2012). Specifically, coplanar polychlorinated biphenyls (PCBs) have been shown to initiate the earliest stages of atherosclerotic plaque formation, e.g., endothelial cell dysfunction and inflammation (Lim et al, 2008; Majkova et al, 2009; Majkova et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling

Han

Toxicology and Applied Pharmacology

et al. 2014

Environmental toxicants such as polychlorinated biphenyls (PCBs) have been implicated in the promotion of multiple inflammatory disorders including cardiovascular disease, but information regarding mechanisms of toxicity and cross-talk between relevant cell signaling pathways is lacking. To examine the hypothesis that cross-talk between membrane domains called caveolae and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways alter PCB-induced inflammation, caveolin-1 was silenced in vascular endothelial cells, resulting in a decreased PCB-induced inflammatory response. Cav-1 silencing (siRNA treatment) also increased levels of Nrf2-ARE transcriptional binding, resulting in higher mRNA levels of the antioxidant genes glutathione s-transferase and NADPH dehydrogenase quinone-1 in both vehicle and PCB-treated systems. Along with this upregulated antioxidant response, Cav-1 siRNA treated cells exhibited decreased mRNA levels of the Nrf2 inhibitory protein Keap1 in both vehicle and PCB-treated samples. Silencing Cav-1 also decreased protein levels of Nrf2 inhibitory proteins Keap1 and Fyn kinase, especially in PCB-treated cells. Further, endothelial cells from wildtype and Cav-1−/− mice were isolated and treated with PCB to better elucidate the role of functional caveolae in PCB-induced endothelial inflammation. Cav-1−/− endothelial cells were protected from PCB-induced cellular dysfunction as evidenced by decreased vascular cell adhesion molecule (VCAM-1) protein induction. Compared to wildtype cells, Cav-1−/− endothelial cells also allowed for a more effective antioxidant response, as observed by higher levels of the antioxidant genes. These data demonstrate novel cross-talk mechanisms between Cav-1 and Nrf2 and implicate the reduction of Cav-1 as a protective mechanism for PCB-induced cellular dysfunction and inflammation.