TY - JOUR
T1 - Acute toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) in male Sprague-Dawley rats
T2 - Effects on hepatic oxidative stress, glutathione and metals status
AU - Lai, Ian
AU - Chai, Yingtao
AU - Simmons, Don
AU - Luthe, Gregor
AU - Coleman, Mitchell C.
AU - Spitz, Douglas
AU - Haschek, Wanda M.
AU - Ludewig, Gabriele
AU - Robertson, Larry W.
N1 - Funding Information:
The authors would like to thank their laboratory colleagues for their assistance with the animal studies and for useful discussions. This study was supported by the Iowa Superfund Basic Research Program ( P42 ES013661 ) from NIEHS. Gregor Luthe received support from Alexander von Humboldt Foundation, Bonn, Germany. Contents reflect the views of the authors and do not represent any official view(s) of NIEHS or NIH. Funds were also available from the Environmental Health Sciences Research Center ( P30 ES05605 ) and the Radiation and Free Radical Research Core lab (P30 CA086862).
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Copper
KW - Glutathione
KW - Morphology
KW - Polychlorinated biphenyls (PCBs)
KW - Redox status
KW - Selenium
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=77957245233&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957245233&partnerID=8YFLogxK
U2 - 10.1016/j.envint.2009.11.002
DO - 10.1016/j.envint.2009.11.002
M3 - Article
C2 - 19969354
AN - SCOPUS:77957245233
SN - 0160-4120
VL - 36
SP - 918
EP - 923
JO - Environment international
JF - Environment international
IS - 8
ER -