DIETARY ANTIOXIDANTS (SELENIUM N-ACETYLCYSTEINE) MODULATE PARAOXONASE 1 (PON1) IN PCB126-EXPOSED RATS

摘要

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.