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TCDD-MEDIATED OXIDATIVE STRESS IN MALE RAT PUPS FOLLOWING PERINATAL EXPOSURE
Citation:
Slezak, B. P., J. T. Hamm, J. Reyna, C. H. Hurst, AND L S. Birnbaum. TCDD-MEDIATED OXIDATIVE STRESS IN MALE RAT PUPS FOLLOWING PERINATAL EXPOSURE. JOURNAL OF BIOCHEMICAL TOXICOLOGY 16(2):49-52, (2002).
Description:
TCDD is a highly persistent trace environmental contaminant and is one of the most potent toxicants known to man. Our laboratory has previously reported an increase in the production of reactive oxygen species (ROS) in the brain of female B6C3F1 mice following subchronic exposure to TCDD at doses as low as 0.45 ng/kg/day (1). In addition, we have demonstrated changes in oxidative stress indicators following subchronic TCDD exposure at doses as low as 0.15 ng TCDD/kg/d in the liver, lung, and kidney (2). Recent studies have also indicated that TCDD may produce a sustained oxidative stress response (3) which may be related to the induction of cytochrome P450s' (4). Hassoun et al (5) demonstrated a modulation of TCDD induced oxidative stress via vitamin E succinate and ellagic acid treatment in embryonic/fetal and placental tissues of C57Bl/6J mice. The role of TCDD mediated oxidative stress in the developing animal is not completely understood and warrants further investigation.
In this study, pregnant Long Evans rats were dosed with 1.0 ?g/kg TCDD on gestational day (GD)15 in order to investigate oxidative stress in the liver of male pups following gestational exposure to TCDD. Lipid peroxidation (TBARS), production of ROS, and total glutathione (GSH) were assayed to identify changes in oxidative stress parameters in the liver during development. Male pup liver was assayed for oxidative stress 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 PND4 and PND25. However, pup hepatic lipid peroxidation was unchanged throughout the time course. In addition, hepatic total GSH levels were not significantly changed although the mean for the TCDD treated groups was less than those of the controls at all time points except PND49. 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.