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

Abstract

Although polychlorinated biphenyl (PCBs) production, and new uses for PCBs, was halted in the 1970s in the United States, PCBs continue to be used in closed systems and persist in the environment, accumulating in fatty tissues. PCBs are efficacious inducers of drug metabolism and may increase oxidative events and alter many other biochemical and morphologic parameters within cells and tissues. The goal of the present study was to evaluate the effects of a single, very low dose of PCB 126 (3,3′,4,4′,5-pentachlorobiphenyl), a coplanar, dioxin-like PCB congener and aryl hydrocarbon receptor (AhR) agonist, on the redox status, metals homeostasis, antioxidant enzymes, and cellular morphology. To examine these parameters, male Sprague-Dawley rats were fed a purified AIN-93 basal diet containing 0.2 ppm selenium for two weeks, then administered a single i.p. injection of corn oil (5 ml/kg body weight) or 1 μmol PCB 126/kg body weight (326 μg/kg body weight) in corn oil. Rats were maintained on the diet for an additional two weeks before being euthanized. This dose of PCB 126 did not later feed intake or growth, but significantly increased liver weight (42%) and hepatic microsomal cytochrome P-450 (CYP1A) enzyme activities (10-40-fold increase). Hepatic zinc, selenium, and glutathione levels were significantly decreased 15%, 30%, and 20%, respectively, by PCB 126. These changes were accompanied by a 25% decrease in selenium-dependent glutathione peroxidase activity. In contrast, hepatic copper levels were increased 40% by PCB 126. PCB 126-induced pathology was characterized by hepatocellular hypertrophy and mild steatosis in the liver and a mild decrease in cortical T-cells in the thymus. This controlled study in rats fed a purified diet shows that even a single, very low dose of PCB 126 that did not alter feed intake or growth, significantly perturbed redox and metals homeostasis and antioxidant and enzyme levels in rodent liver.

Analysis of plasma indices of redox homeostasis in dairy cows reared in polluted areas of Piedmont (northern Italy)

“…These findings agree with the data previously obtained in buffalo cows (Spagnuolo et al, 2011), as well as in other laboratory species exposed to either 2,3,7,8 tetrachloro-dibenzo-p-dioxin (Stohs et al, 1984;Hassoun et al, 1998;Slezak et al, 2002) or to DL-PCBs (Lai et al, 2010), and support the hypothesis that the exposure to environmental pollutants, such as dioxins, severely impairs the blood antioxidant defence system. As expected, we found that the lower antioxidant capacity, observed in exposed cows, is associated with a significantly higher extent of oxidative modifications of protein and lipid.…”

Oxidative stress in the blood of pregnant rats and reduction of organ weights caused by the polychlorinated biphenyl congener 77

“…The body weight increase of the treated animals was lower than that of the controls in both periods (Table 2). By comparison, it is worth noting that no considerable change was detected in the organ and body weights of rats treated with PCB 126 (3,3 0 ,4,4 0 ,5-pentachlorobiphenyl), a PCB 77 analog (Lai et al 2010). Among organ weight changes, the decrease in heart weight can be attributed to the more intensive work of animals treated on days 8-18, but this change was not detectable in animals treated in the short period on days 1-7.…”

Hepatic oxidative status and metal homeostasis disturbance of 2-hydroxylated dioxin in ICR mice

“…The hepatic zinc levels decreased in the liver of the BDE-15-treated group, whereas they increased in the CDE-15-treated and the HODE-15-treated groups (Zhang et al, 2014b). Lai et al (2010) found that the hepatic copper levels were increased by 40% and the hepatic zinc levels were decreased by 15% after two weeks of exposure to 1 mol/kg of PCB-126. Furthermore, the changes in the metal levels were also related to the oxidative status in the organisms.…”