PubMed2002
The mechanism of toxicity of structurally diverse environmental toxicants including heavy metals and polyhalogenated and polycyclic 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 LD(50) 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 LD(50) 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 LD(50) and 0.01 LD(50) 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 LD(50) 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 LD(50) 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 LD(50) 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 LD(50) doses. Lesser effects were observed with 0.10 and 0.01 LD(50) doses of these xenobiotics as compared to the 0.50 LD(50) 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.