Comparative effects of TCDD, endrin, naphthalene and chromium (VI) on oxidative stress and tissue damage in the liver and brain tissues of mice

The mechanism of toxicity of structurally diverse environmental toxicants including heady metals and poly halogenated and polycylclic hydrocarbons may involve a common cascade of events which entails an oxidative stress and production of reactive oxygen species. We have determined the comparative effects of single 0.01. 0.10 and 0.50 LD50 doses of 2.3.7.8-tetrachlorodibenzo-p-dioxin (TCDD). endrin, naphthalene and sodium dichromate (chromium VI) on lipid peroxidation. DNA fragmentation and enhanced production of superoxide anion (cytochrome c reduction) in liver and brain tissues of C57BL/6NTac mice. The effects of a single acute oral 0.50 LD50 dose of these xenobiotics on hepatic and brain lipid peroxidation were investigated at 0. 12. 24. 48, and 96 h after treatment, while the effects of 0.10 LD50 and 0.01 LD50 doses of these xenobiotics were at 0, 24. 48. 72, and 96 h after treatment. Dose- and time-dependent effects were observed with all four xenobiotics. At a 0.50 LD50 dose of TCDD. endrin. naphthalene and chromium VI, maximum increases in cytochrome c reduction (superoxide anion production) of approximately 5.7-, 5.4- 5.3- and 4.1-fold. respectively. were observed in hepatic tissues. TCDD showed an increasing effect through 96 h. Endrin and naphthalene demonstrated a maximum effect at 12-24 h. while chromium VI exhibited a maximum effect at 48 h. With respect to lipid peroxidation. at a 0.50 LD50 dose both endrin and chromium VI induced the maximum effect at 48 h of treatment. while naphthalene demonstrated the maximum effect after 24 h of treatment. TCDD demonstrated a continued effect through 96 h of treatment. At a 0.50 LD50 dose TCDD. endrin. naphthalene and chromium VI produced maximum increases in hepatic lipid peroxidation of approximately 3.5-, 3.1-, 3.7- and 3.3-fold in hepatic tissues. respectively. Similar results were obtained in hepatic and brain DNA fragmentation at 0.50 LD50 doses. Lesser effects were observed with 0.10 and 0.01 LD50 doses of these xenobiotics as compared to the 0.50 LD50 dose. The results clearly demonstrate that these diverse xenobiotics induce dose- and time-dependent oxidative stress and tissue damage in the liver and brain tissues of mice. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.