TCDD-mediated oxidative stress in male rat pups following perinatal exposure.
2,3,7,8-tetrachlorododibenzo-p-dioxin (TCDD) is a highly persistent trace environmental contaminant and is one of the most potent toxicants known. Exposure to TCDD has been shown to cause oxidative stress in a variety of animal models. In this study, pregnant Long Evans rats were dosed with 1 microg TCDD/kg on gestational day (GD) 15 so as to investigate oxidative stress in the liver of male pups following gestational exposure to TCDD. Lipid peroxidation (TBARS), production of reactive oxygen species (ROS), and total glutathione (GSH) were assayed to identify changes in oxidative stress parameters in the pup liver at GD 21 and postnatal days (PND) 4, 25, 32, 49, and 63. Mean ROS levels in pups were elevated at all time points tested with a significant elevation at PND 4 and PND 25. However, pup hepatic lipid peroxidation was unchanged throughout the time course. In addition, hepatic total GSH levels were not significantly changed although the means for the TCDD-treated groups were less than those of the controls at all time points except PND 49. The results indicate that although the levels of ROS are increased following gestational/lactational exposure, this increase does not translate to direct oxidative damage or significant changes to endogenous antioxidant defense mechanisms. Further investigation into the effect of gestational/lactational exposure in pups should include additional endpoints for further characterization of the time course of the response, the effect upon extrahepatic tissues, and investigation of differences between male and female offspring.
Slezak
B P
BP
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hamm
J T
JT
Reyna
J
J
Hurst
C H
CH
Birnbaum
L S
LS
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure; D008862:Microsomes, Liver / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000032:analysis
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D017382:Reactive Oxygen Species; D019363:Cytochrome P-450 CYP1A1; D005978:Glutathione