Modulation of Selenium-Dependent Glutathione Peroxidase by Perfluorodecanoic Acid in Rats: Effect of Dietary Selenium

Abstract

Forty-eight male Sprague-Dawley rats fed a diet containing 0.4, 0.2 or 1.0 mg of selenium (Se)/kg of diet were injected with a single dose (35 mg/kg) of perfluorodecanoic acid (PFDA) in corn oil and killed 2 wk later. Control animals were pair-fed and treated with an equal volume of vehicle. PFDA treatment significantly increased Se-dependent glutathione peroxidase (Se-GSHPx) activity in liver cytosol of rats fed the 0.04 mg of Se/kg of diet but not in rats fed the other diets. The increase in liver cytosolic Se-GSHPx activity in rats fed 0.04 mg of Se/kg of diet paralleled increases in Se content and serum Se-GSHPx activity. Determination of Se-GSHPx by an enzyme-linked immunosorbent assay showed that PFDA caused a decrease in Se-GSHPx protein in rats fed 0.2 or 1.0 mg of Se/kg of diet but not in rats fed 0.04 mg of Se/kg of diet. Further analysis revealed that the ratio of Se-GSHPx activity to antibody-reactive protein was increased by PFDA in all three groups. The in vitro addition of PFDA directly to the assay mixture for Se-GSHPx activity did not produce any effect. Reduced glutathione was significantly increased by PFDA treatment in all three groups. These data show that PFDA affects the Se content, Se-GSHPx activity and Se-GSHPx protein in rat liver and that the effect is dependent on the dietary/hepatic Se level.

Peroxisome proliferator perfluorodecanoic acid alters glutathione and related enzymes

“…As expected, hepatic GSH levels were elevated in rats treated with a single dose of PFDA as in the previous report [14]. This response of GSH, however, was not uniformly observed in treatments with various peroxisome proliferators.…”

“…Previously, we have shown that PFDA treatment significantly increased hepatic GSH levels in rats without significantly altering selenium-GSHPx activity [14]. The purpose of this study was to examine if PFDA treatment causes elevation of GSH in rat liver by altering the activities of enzymes that regulate GSH homeostasis.…”

“…Contrast to many peroxisome proliferators, PFDA treatment lowers the flux through peroxisomal b-oxidation, even though it induced peroxisomal FAO activity as other peroxisome proliferators [32,33]. PFDA inhibits several enzymes involved in peroxisomal b-oxidation, which may decrease the rate of peroxisomal b-oxidation and H 2 0 2 production [34], but it had no effect on GSHPX [14]. Decreased activity of cytosolic GSTs, a family of GSH-utilizing enzymes, following PFDA treatment observed in this study is consistent with the other reports [35][36][37][38].…”

“…Other housing conditions were essentially the same as in the previous experiment by Chen et al [14]. Rats were fed a commercial diet and water ad libitum.…”

Acute toxicity of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) in male Sprague–Dawley rats: Effects on hepatic oxidative stress, glutathione and metals status

“…Rats were fed a purified AIN-93 basal diet containing 0.2 ppm sodium selenate (Table 1; Harland Teklad, Madison, WI) and water ad libitum . A purified diet with a carefully controlled selenium level was chosen for this study, since previously we had observed that dietary selenium could directly influence the outcome of studies of the regulation of SeGPx (Chen et al 1990). After two weeks on the diet, rats were administered a single i.p.…”