Oxidative Stress in Female B6C3F1 Mice following Acute and Subchronic Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)

• Published in: Toxicological sciences 2000-04, Vol.54 (2), p.390-398
• Main Authors: Slezak, B. P., Hatch, G. E., DeVito, M. J., Diliberto, J. J., Slade, R., Crissman, K., Hassoun, E., Birnbaum, L. S.
• Format: Article
• Language: English
• Subjects: Animals; Ascorbic Acid - metabolism; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Environmental Pollutants - metabolism; Environmental Pollutants - toxicity; Female; Glutathione - metabolism; Kidney - drug effects; Kidney - metabolism; Liver - drug effects; Liver - metabolism; Lung - drug effects; Lung - metabolism; Medical sciences; Mice; Mice, Inbred Strains; oxidative stress; Oxidative Stress - drug effects; oxygen; Polychlorinated Dibenzodioxins - metabolism; Polychlorinated Dibenzodioxins - toxicity; reactive oxygen species (ROS); Spleen - drug effects; Spleen - metabolism; Superoxides - metabolism; TCDD; Thiobarbituric Acid Reactive Substances - metabolism; Time Factors; Tissue Distribution; Toxicology; Various organic compounds
• ISSN: 1096-6080; 1096-0929; 1096-0929
• DOI: 10.1093/toxsci/54.2.390

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly persistent trace environmental contaminant and is one of the most potent toxicants known to man. Hassoun et al. (1998, Toxicol. Sci. 42, 23–27) 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. In the present study, oxidative stress was characterized in liver, spleen, lung, and kidney following subchronic (0.15–150 ng/kg; 5 days/week for 13 weeks, po) or acute exposure (0.001–100 μg/kg, po) to TCDD in order to investigate the interaction between tissue concentration and time for production of ROS. Seven days following acute administration of TCDD, mice were sacrificed; they demonstrated increases in liver superoxide anion production (SOAP) and thiobarbituric acid reactive substances (TBARS) at doses of 10 and 100 μg/kg, associated with hepatic TCDD concentrations of 55 and 321 ng/g, respectively. Liver obtained from mice following subchronic TCDD exposure demonstrated an increase in SOAP and TBARS above controls at doses of 150 ng/kg/day with liver TCDD concentration of only 12 ng/g. Interestingly, glutathione (GSH) levels in lung and kidney following subchronic TCDD exposure were decreased at the low dose of 0.15 ng/kg/day. This effect disappeared at higher TCDD doses. The data suggest that higher tissue TCDD concentrations are required to elicit oxidative stress following acute dosing than with subchronic TCDD exposure. Therefore, the mechanism of ROS production following TCDD exposure does not appear to be solely dependent upon the concentration of TCDD within the tissue. In addition, very low doses of TCDD that result in tissue concentrations similar to the background levels found in the human population produced an effect on an oxidative stress endogenous defense system. The role of this effect in TCDD-mediated toxicity is not known and warrants further investigation.