Production of superoxide anion, lipid peroxidation and DNA damage in the hepatic and brain tissues of rats after subchronic exposure to mixtures of TCDD and its congeners

• Published in: Journal of applied toxicology Vol. 21; no. 3; pp. 211 - 219
• Main Authors: Hassoun, Ezdihar A., Li, Feng, Abushaban, Ahmed, Stohs, Sidney J.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-05-2001; Wiley
• Subjects: Animals; Biological and medical sciences; Biomarkers - analysis; brain; Brain - drug effects; Brain - pathology; Chemical and industrial products toxicology. Toxic occupational diseases; DNA Damage; Dose-Response Relationship, Drug; Environmental Pollutants - toxicity; Female; Lipid Peroxidation; liver; Liver - drug effects; Liver - pathology; Medical sciences; Oxidative Stress; Polychlorinated Dibenzodioxins - toxicity; Rats; Rats, Sprague-Dawley; Superoxides; TCDD; TCDD congeners; TEQ; Toxicology; Various organic compounds; Oxidative stress; Subchronic; Rat; Toxicity; Liver; Central nervous system; Lipids; Oxygen heterocycle; Toxic association; Dose activity relation; Chlorine Organic compounds; Aromatic compound; Oxidation; Peroxidation; Poison interaction; Rodentia; Polychlorobiphenyl; Vertebrata; Hyperoxides; Mammalia; Single strand break; Animal; DNA; Digestive diseases; Brain (vertebrata)
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.744

In this study the induction of oxidative stress in the hepatic and brain tissues of rats after subchronic exposure to various mixtures of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) and two of its congeners, namely 2,3,4,7,8‐pentachlorodibenzofuran (PeCDF) and 3,3′,4,4′,5‐pentachlorobiphenyl (PCB 126) was investigated. Four mixtures of TCDD and its congeners, corresponding to 10, 22, 46 and 100 ng of toxic equivalence (TEQ) kg−1 day−1, were administered to groups of rats for 13 weeks. The animals were sacrificed at the end of the exposure period and the biomarkers of oxidative stress, including the production of superoxide anion, lipid peroxidation and DNA single‐strand breaks (SSBs), were determined in the hepatic and brain tissues. All mixtures caused dose‐dependent increases in the production of superoxide anion, lipid peroxidation and DNA SSBs in both tissues, with significantly higher damage in the hepatic compared with the brain tissues. The 22 ng TEQ dose level (TEQ = 22) contains TCDD, PeCDF and PCB 126 at levels that correspond to 7.3, 14.5 and 73.3 ng kg−1 day−1, respectively, and it produced effects that correspond to ca. 50% of the maximal production of superoxide anion, lipid peroxidation and DNA SSBs in the hepatic and brain tissues of those animals. Relative to the doses that are required to produce 50% of the maximal production of the biomarkers of oxidative stress by the individual congeners in hepatic and brain tissues of rats, the concentrations of the congeners in TEQ = 22 did result in significant interactivity, probably in the form of additive effects in the hepatic but not in brain tissues. Copyright © 2001 John Wiley & Sons, Ltd.