Dietary antioxidants (selenium and N-acetylcysteine) modulate paraoxonase 1 (PON1) in PCB 126-exposed rats

Abstract

The environmental pollutants polychlorinated biphenyls (PCBs), especially dioxin-like PCBs, cause oxidative stress and associated toxic effects, including cancer and possibly atherosclerosis. We previously reported that PCB 126, the most potent dioxin-like PCB congener, decreases antioxidants such as hepatic selenium (Se), selenium-dependent glutathione peroxidase and glutathione (GSH), but also increases levels of the anti-atherosclerosis enzyme paraoxonase 1 (PON1) in liver and serum. To probe the interconnection of these three antioxidant systems, Se, GSH, and PON1, we examined the influence of varying levels of dietary Se and N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS) and precursor for GSH synthesis, on PON1 in the absence and presence of PCB 126 exposure. Male Sprague Dawley rats, fed diets with differing Se levels (0.02, 0.2, or 2 ppm) or NAC (1%), were treated with a single intraperitoneal injection of corn oil or various doses of PCB 126 and euthanized 2 weeks later. PCB126 significantly increased liver PON1 mRNA, protein level and activity and serum PON1 activity in all dietary groups, but did not consistently increase thiobarbituric acid levels (TBARS), an indicator for lipid oxidation and oxidative stress, in liver or serum. Inadequate (high or low) dietary Se decreased baseline and PCB 126-induced aryl hydrocarbon receptor expression but further increased PCB 126-induced cytochrome P450 1A1 expression, the enzyme believed to be the cause for PCB 126-induced oxidative stress. In addition, a significant inverse relationship was observed between dietary Se levels and PON1 mRNA and PON1 activity, but also with TBARS levels in the liver, suggesting significant antioxidant protection from dietary Se. NAC lowered serum baseline TBARS levels in the controls and increased serum PON1 activity but lowered liver PON1 activities in animals treated with 1 μmol/kg PCB 126, suggesting antioxidant activity by NAC primarily in serum. These results also show an unexpectedly predominantly inverse relationship between Se or NAC and PON1 during normal and PCB 126 exposure conditions. These interactions should to be further explored in the development of dietary protection regimens.

Sustained expression of CYPs and DNA adduct accumulation with continuous exposure to PCB126 and PCB153 through a new delivery method: Polymeric implants

“…Paraoxon and phenylacetate were used as two individual substrates in PON1 activity measurements as described [27] . Briefly, the enzyme activities were determined spectrophotometrically following the initial rate of substrate hydrolysis to p-nitrophenol (412 nm) or phenol (270 nm), respectively.…”

Phenotypes and concentration of PON1 in cardiovascular disease: The role of nutrient intake

“…Several in-vivo studies have shown an increase in PON1 activity/expression following vitamin C consumption [11], vitamin E consumption [12], carotenoids [13], mono-and polyunsaturated fatty acids [14], selenium consumption [15], and polyphenol supplementation [16].…”

Regulatory effects of dioxin-like and non-dioxin-like PCBs and other AhR ligands on the antioxidant enzymes paraoxonase 1/2/3

“…Paraoxonases are important antioxidant enzymes in tissues and blood and our previous studies indicated that at least one PCB congener, PCB126, the most potent AhR agonist among all PCBs, can influence the PON1 gene expression and enzyme activity levels in rats (Shen et al 2014, Shen et al 2012). This raised two questions: 1.…”

“…However this potential chemoprotection option needs to be carefully approached as our results with N-acetyl cysteine and selenium in PCB126 exposed rats have shown (Shen et al 2014). …”

“…Our earlier studies demonstrated that the dioxin-like PCB 126 (3,3′,4,4′,5-pentachlorobiphenyl) significantly increased PON1 activity in liver and serum of rats and PON1 gene expression in the liver (Shen et al 2012). This increase was independent of the route of exposure (Aqil et al 2014) or the diet (Shen et al 2014). In this study, we asked whether non-dioxin-like PCBs or other AhR agonists affect the regulation of PON1.…”