Suppression of endogenous antioxidant enzymes by 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in chicken liver during development

Domestic chickens (Gallus gallus) are an excellent model in which to evaluate developmental toxicity and oxidative stress because of their high sensitivity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The goal of this study was to measure the effects of environmentally relevant doses of TCDD on endogenous hepatic antioxidant enzyme activity in hatchling chickens. The vehicle (sunflower oil) or 2, 20, or 200 pg/g TCDD was injected into chicken eggs before incubation. On hatching, livers were harvested and quickly frozen. The changes in activity of antioxidant enzymes, including glutathione peroxidase (GPx), glutathione reductase (GRx), copper zinc superoxide dismutase (SOD), and catalase (CAT) were determined as indicators of oxidative stress. TCDD exposure was associated with a significant suppression of the activities of the protective endogenous enzymes GPx, GRx, and SOD in the liver, even at the lowest dose. CAT activity was also suppressed, but not significantly. The measured decreases were 37% to 63% for GPx, 50% to 58% for GRx, 30% to 40% for SOD, and 16% to 24% for CAT. Noncomplex dose-response relationships were evident in GPx and GRx, whereas SOD and CAT curves were U-shaped. These results demonstrate that a decreased ability to scavenge reactive oxygen species may result from developmental TCDD exposure at very low doses, contributing to oxidative stress and thus to the embryotoxicity of TCDD.