Bagchi D, Bagchi M, Hassoun E, Stohs S J
School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178.
Pharmacology. 1993 Sep;47(3):209-16. doi: 10.1159/000139099.
Previous studies have demonstrated that the hepatotoxin carbon tetrachloride rapidly promotes lipid peroxidation and inhibits microsomal calcium sequestration, microsomal glucose-6-phosphatase activity and cytochrome P-450. Due to its profound effects on lipid peroxidation, we have examined the oral administration of 2.5 ml/kg carbon tetrachloride on the urinary excretion of the lipid metabolites formaldehyde, malondialdehyde, acetaldehyde and acetone. Urine samples were collected up to 48 h after treatment. The urinary metabolites were identified and quantitated by gas chromatography-mass spectrometry and high-pressure liquid chromatography. Time-dependent increases in the urinary excretion of the four metabolites were observed after carbon tetrachloride administration. At 48 h after treatment, the increases in the excretion of malondialdehyde, formaldehyde, acetaldehyde and acetone were approximately 55, 78, 57 and 268%, respectively, relative to control values. The data were expressed in nanomoles per kilogram body weight per 4.5 h. The results clearly demonstrate that carbon tetrachloride increases the urinary excretion of four lipid metabolites which may serve as noninvasive biomarkers of xenobiotic-induced lipid peroxidation.
先前的研究表明,肝毒素四氯化碳能迅速促进脂质过氧化,并抑制微粒体钙螯合、微粒体葡萄糖-6-磷酸酶活性和细胞色素P-450。鉴于其对脂质过氧化的深远影响,我们研究了口服2.5毫升/千克四氯化碳对脂质代谢产物甲醛、丙二醛、乙醛和丙酮尿排泄的影响。在治疗后长达48小时收集尿液样本。通过气相色谱-质谱联用仪和高压液相色谱对尿代谢产物进行鉴定和定量。给予四氯化碳后,观察到四种代谢产物的尿排泄呈时间依赖性增加。治疗后48小时,丙二醛、甲醛、乙醛和丙酮排泄量相对于对照值分别增加了约55%、78%、57%和268%。数据以每4.5小时每千克体重的纳摩尔数表示。结果清楚地表明,四氯化碳增加了四种脂质代谢产物的尿排泄,这些代谢产物可能作为异源物质诱导脂质过氧化的非侵入性生物标志物。