Role of oxidative stress in the promoting activities of PCBs

Abstract

PCBs are organic pollutants that persist and bioaccumulate in the environment. These chemicals induce and promote liver tumors in rodents. Previous studies have shown that they increase oxidative stress in the liver, including lipid peroxidation, oxidative DNA damage, and NF-κB activation. The objective of these studies was to determine if the promoting activities of PCBs could be inhibited by dietary antioxidants (vitamin E, selenium, or phytochemicals) or by knocking out the p50 subunit of NF-κB. In the antioxidant studies, female rats were first injected with DEN (150 mg/kg) and then administered 4 biweekly i.p. injections (300 μmol/kg/injection) of PCB-77, PCB-153, or vehicle; the number and volume of placental glutathione S-transferase (PGST)-positive foci were then quantified. Vitamin E did not influence the promoting activities of PCBs. Increasing dietary selenium above the recommended intake increased the number of foci induced but decreased their volume. Most of the phytochemicals examined (N-acetyl cysteine, β-carotene, resveratrol, EGCG) had no significant effect on the promoting activity of PCB-77. Ellagic acid increased and lycopene decreased the number of foci; ellagic acid, CoQ 10 , and curcumin decreased the volume of foci. In the NF-κB knockout study, male mice were first injected with DEN (90 mg/kg); controls not receiving DEN were also studied. Both p50 −/− and wild-type mice were then injected biweekly 20 times with PCB-153 (300 (μmol/kg). In DEN-treated and DEN + PCB-treated mice, the incidence of tumors was lower in the p50 −/− mice than in wild-type mice. In mice receiving PCB-153, the tumor incidence and tumor volume were higher. The volume of tumors that were positive for glutamine synthetase was increased in mice administered PCB-153. This study shows that the promotion of hepatocarcinogenesis by PCBs is largely unaffected by dietary antioxidants but is diminished when NF-κB activation is impaired by the absence of the p50 subunit.

DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells

“…In this respect, in a recent study, Alegría-Torres et al (Frigo et al, 2004;Kim et al, 2004). Similar findings were found for PCBs (Bezdecny et al, 2007;Glauert et al, 2008;Myhre et al, 2009;Wang et al, 2008). In line with the mechanism proposed by Champion et al (2013), our data showed that the over-expression of AhR was dependent on the TNF induced by DDE and PCB 153.…”

“…Those findings indicated that AhR expression in FLSs was stimulated in the presence of TNF, similar to our results here. Taking into account that data and our own, we hypothesize that TNF induced by DDE and PCB 153 (Alegría-Torres et al 2009; Cárdenas-González et al, 2013), likely via an NF-B pathway (Bezdecny et al, 2007;Frigo et al, 2004;Glauert et al, 2008;Kim et al, 2004;Myhre et al, 2009;Wang et al, 2008), was able to induce AhR mRNA expression.…”

Effects of exposure to BDE-99 on oxidative status of liver and kidney in adult rats

“…In this study, we proposed an oxidative stress-like mechanism inductor of hepatic and renal damage after acute oral administration of BDE-99 in adult male rats. This hypothesis was based on the results of recent studies showing that exposure to certain environmental toxicants such as PCBs, caused disorders through oxidative damage in rodents (Schlezinger et al, 2006;Glauert et al, 2008).…”

Synthesis and characterization of thermally responsive N-isopropylacrylamide hydrogels copolymerized with novel hydrophobic polyphenolic crosslinkers

“…Additionally, curcumin has shown significant impact in reducing oxidative stress induced by environmental pollutants such as metal nanoparticles, polychlorinated biphenyls (PCBs), etc. [36, 37]. Furthermore, our recent efforts found that curcumin, and potentially other polyphenols (e.g., quercetin), have shown binding affinities to environmental contaminants (e.g., PCBs).…”