Bagchi D, Shara M A, Bagchi M, Hassoun E A, Stohs S J
Department of Pharmaceutical Sciences, Creighton University Health Sciences Center, Omaha, Nebraska 68178.
Toxicol Appl Pharmacol. 1993 Nov;123(1):83-8. doi: 10.1006/taap.1993.1224.
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 micrograms/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.
2,3,7,8-四氯二苯并对二恶英（TCDD）产生脂质动员和改变脂质代谢的能力是众所周知的。先前的研究表明，TCDD会诱导氧化应激并增强脂质过氧化。然而，响应TCDD而改变的脂质代谢所产生的产物尚未得到研究。我们检测了大鼠单次口服50微克/千克剂量的TCDD后，血清和尿液中丙二醛、甲醛、乙醛和丙酮水平随时间的变化。通过高压液相色谱法（HPLC）对这四种代谢产物的变化进行定量。在随意进食的对照动物和配对喂养的动物中比较了TCDD的作用。在第0、3、6、9和12天测定血清和尿液中四种代谢物的水平。给予TCDD后，在所有时间点均观察到血清和尿液中四种代谢物的显著增加。例如，在治疗后第6天，相对于配对喂养的对照动物，血清中的丙二醛、甲醛、乙醛和丙酮分别增加了约1.8倍、1.4倍、2.0倍和3.0倍，尿液中分别增加了1.3倍、1.4倍、1.6倍和2.0倍。在大多数时间点，TCDD处理动物的血清和尿液中四种代谢物水平的增加显著高于配对喂养的对照动物。当将HPLC测定的血清丙二醛水平与硫代巴比妥酸（TBA）比色法获得的结果进行比较时，观察到相似的时间进程，尽管特异性较低的TBA方法获得的结果更高。结果清楚地表明，TCDD导致与脂质代谢相关的四种特定产物的血清和尿液水平显著升高。
