Dietary selenium as a modulator of PCB 126-induced hepatotoxicity in male Sprague-Dawley rats

Abstract

Homeostasis of selenium (Se), a critical antioxidant incorporated into amino acids and enzymes, is disrupted by exposure to aryl hydrocarbon receptor (AhR) agonists. Here we examined the importance of dietary Se in preventing the toxicity of the most toxic polychlorinated biphenyl congener, 3,3',4,4',5-pentachlorobiphenyl (PCB 126), a potent AhR agonist. Male Sprague-Dawley rats were fed a modified AIN-93 diet with differing dietary Se levels (0.02, 0.2, and 2 ppm). Following 3 weeks of acclimatization, rats from each dietary group were given a single ip injection of corn oil (vehicle), 0.2, 1, or 5 μmol/kg body weight PCB 126, followed 2 weeks later by euthanasia. PCB exposure caused dose-dependent increases in liver weight and at the highest PCB 126 dose decreases in whole body weight gains. Hepatic cytochrome P-450 (CYP1A1) activity was significantly increased even at the lowest dose of PCB 126, indicating potent AhR activation. PCB exposure diminished hepatic Se levels in a dose-dependent manner, and this was accompanied by diminished Se-dependent glutathione peroxidase activity. Both these effects were partially mitigated by Se supplementation. Conversely, thioredoxin (Trx) reductase activity and Trx oxidation state, although significantly diminished in the lowest dietary Se groups, were not affected by PCB exposure. In addition, PCB 126-induced changes in hepatic copper, iron, manganese, and zinc were observed. These results demonstrate that supplemental dietary Se was not able to completely prevent the toxicity caused by PCB 126 but was able to increase moderately the levels of several key antioxidants, thereby maintaining them roughly at normal levels.

FIG. 1.

Liver Se (μg/g tissue) under each experiment condition and significance of various comparisons (adjusted using Dunnett’s test). Results are expressed as mean ± SEM (n = 4–6 animals/group). One-way ANOVA was used to examine the difference between each PCB 126 level and the corresponding corn oil treatment (*) and low (0.02) or supplemented (2 ppm)-Se level versus adequate (0.2 ppm) Se level (#). p < 0.05.

FIG. 2.

SeGPx activity (μmol/min/mg protein) and significance of various comparisons (adjusted using Dunnett’s test). Results are expressed as mean ± SEM. Each group contained four to six animals. One-way ANOVA was used to examine the difference between each PCB 126 level and the corn oil treatment (*) and between low/high Se and the adequate Se control (#). p < 0.05.

FIG. 3.

TrxR activity (U/ml) under each experiment condition and significance of various comparisons (adjusted using Dunnett’s test). Results are expressed as mean ± SEM. Each group contained four to six animals. One-way ANOVA was used to examine the difference between each PCB 126 level and the corn oil treatment. “*” Indicates significant differences of PCB treatments versus corn oil vehicle control; “#” indicates significant difference of low/high Se versus adequate Se. p < 0.05.

FIG. 4.

Trx1 (top) and Trx2 (bottom) oxidation state and significance of various comparisons (adjusted using Dunnett’s test). Results are expressed as mean ± SEM. Each group contained three animals. One-way ANOVA was used to examine the difference between each PCB 126 level and the corn oil treatment (*) and low/supplemented Se versus 0.2 ppm dietary Se (#); p < 0.05.