Time-Dependent Effects of 2,3,7,8-Tetrachlorodibenzo- p-dioxin on Serum and Urine Levels of Malondialdehyde, Formaldehyde, Acetaldehyde, and Acetone in Rats

Abstract

The ability of TCDD to produce lipid mobilization and alter lipid metabolism is well known. Previous studies have indicated that TCDD induces an oxidative stress and enhances lipid peroxidation. However, the products resulting from altered lipid metabolism in response to TCDD have not been studied. We have examined the time-dependent changes in serum and urine levels of malondialdehyde, formaldehyde, acetaldehyde, and acetone in response to a single oral 50 μg/kg dose of TCDD in rats. The changes in these four metabolic products were quantitated by high-pressure liquid chromatography (HPLC). The effects of TCDD were compared in ad libitum-fed control animals and pair-fed animals. Serum and urine levels of the four metabolites were assayed on Days 0, 3, 6, 9, and 12. Following TCDD administration, significant increases in the four metabolites present in serum and urine were observed at all time points. For example, on Day 6 post-treatment malondialdehyde, formaldehyde, acetaldehyde, and acetone increased approximately 1.8-, 1.4-, 2.0-, and 3.0-fold in serum, respectively, and 1.3-, 1.4-,1.6-, and 2.0-fold in urine, respectively, relative to pair-fed control animals. Increases in the serum and urine levels of the four metabolites were significantly greater for TCDD animals than for pair-fed control animals at most time points. When the serum levels of malondialdehyde as determined by HPLC were compared with the results obtained by the thiobarbituric acid (TBA) colorimetric method, similar time courses were observed although higher results were obtained for the less specific TBA method. The results clearly demonstrate that TCDD causes markedly elevated serum and urine levels of four specific products associated with lipid metabolism.