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.
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 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 1µmol PCB 126/kg body weight (326µg/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 alter 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 60% 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.
Lai
Ian
I
Department of Occupational & Environmental Health, Interdisciplinary Graduate Program in Human Toxicology, College of Public Health, University of Iowa, Iowa City, Iowa 52242-5000, United States.
Chai
Yingtao
Y
Simmons
Don
D
Luthe
Gregor
G
Coleman
Mitchell C
MC
Spitz
Douglas
D
Haschek
Wanda M
WM
Ludewig
Gabriele
G
Robertson
Larry W
LW
D000818:Animals; D003314:Corn Oil / Q000008:administration & dosage; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism*; D007275:Injections, Intravenous; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008670:Metals / Q000378:metabolism*; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004785:Environmental Pollutants; D008670:Metals; D009153:Mutagens; D003314:Corn Oil; D011078:Polychlorinated Biphenyls; D005978:Glutathione; C023035:3,4,5,3',4'-pentachlorobiphenyl