Hamdan H, Stacey N H
Toxicology Unit, University of Sydney, NSW, Australia.
Toxicol Appl Pharmacol. 1993 Aug;121(2):291-5. doi: 10.1006/taap.1993.1156.
The temporal relationship between trichloroethylene (TRI) and individual serum bile acids (SBA) has been investigated to gain insight into the mechanism of solvent-induced increases in SBA. Male Sprague-Dawley rats were treated with 1 mmol/kg TRI in corn oil, while control rats received only corn oil. Blood samples were collected from the abdominal aorta at 2, 4, 8, and 16 hr after dosing. Individual SBA were determined by high-performance liquid chromatography (HPLC). Liver and blood concentrations of TRI and one of its metabolites, trichloroethanol (TCEOH), were determined by gas chromatography. SBA levels reached their peak at 4 hr and returned to control levels by 16 hr. There was a relationship between SBA levels and TRI concentrations, which were also at their peak 4 hr after dosing. By 16 hr the levels were undetectable. However, peak blood concentrations of TCEOH were reached 8 hr after dosing, and remained high at 16 hr. Cholic acid and taurocholic acid showed the highest levels of bile acids. Some other bile acids were also elevated, including deoxycholic acid, taurodeoxycholic acid, ursodeoxycholic acid, chenodeoxycholic acid, and taurochenodeoxycholic acid. Determination of total bile acids in serum using an enzymatic/colorimetric method showed a similar pattern of response to that obtained with the HPLC analysis. The data are consistent with TRI having a rapid and specific effect on SBA levels by a mechanism other than liver cell damage.
研究了三氯乙烯（TRI）与个体血清胆汁酸（SBA）之间的时间关系，以深入了解溶剂诱导SBA升高的机制。将雄性Sprague-Dawley大鼠用1 mmol/kg的TRI溶于玉米油中进行处理，而对照大鼠仅接受玉米油。给药后2、4、8和16小时从腹主动脉采集血样。通过高效液相色谱法（HPLC）测定个体SBA。通过气相色谱法测定肝脏和血液中TRI及其一种代谢物三氯乙醇（TCEOH）的浓度。SBA水平在4小时达到峰值，并在16小时恢复到对照水平。SBA水平与TRI浓度之间存在关系，给药后4小时TRI浓度也达到峰值。到16小时时，这些水平无法检测到。然而，TCEOH的血药浓度峰值在给药后8小时达到，并在16小时时仍保持较高水平。胆酸和牛磺胆酸显示出最高的胆汁酸水平。其他一些胆汁酸也有所升高，包括脱氧胆酸、牛磺脱氧胆酸、熊去氧胆酸、鹅去氧胆酸和牛磺鹅去氧胆酸。使用酶促/比色法测定血清中的总胆汁酸显示出与HPLC分析相似的反应模式。这些数据与TRI通过肝细胞损伤以外的机制对SBA水平产生快速且特异性的影响一致。
