Chakrabarti S
Res Commun Chem Pathol Pharmacol. 1986 Aug;53(2):203-11.
Exposure to styrene (S), trichloroethylene (TCE), and carbon tetrachloride (CT) is known to produce hepatotoxic effects in animals and humans. Warfarin (W), the coumarin anticoagulant, is mostly eliminated by hepatic biotransformation and the site of its anticoagulant action is located in the liver. Therefore, the effects of the above solvents on the anticoagulant response to W were studied in male Sprague-Dawley rats. Groups of rats were given i.p. injections of either S (6 and 12 mmole/kg) or TCE (5.6 and 11.2 mmole/kg) or CT (1 mmole/kg) in corn oil 24 h prior to or simultaneously with W (1 mg/kg, s.c.) and the animals were sacrificed 24 h after W. Doses of solvents used in this study showed hepatotoxic effects as verified by significant increases in serum transaminases response. A significant increase in prothrombin time (P.T.) was seen when W was treated simultaneously with S or TCE at any dose level, but not so with CT. An increase in the P.T. of W was also noticed in the groups pretreated with the highest dose of S or TCE and with CT group. Solvents alone had no effect on the P.T. So, acute exposure to organic solvents may lead to enhanced anticoagulant response to W.
已知接触苯乙烯（S）、三氯乙烯（TCE）和四氯化碳（CT）会在动物和人类中产生肝毒性作用。香豆素抗凝剂华法林（W）主要通过肝脏生物转化消除，其抗凝作用部位位于肝脏。因此，在雄性斯普拉格 - 道利大鼠中研究了上述溶剂对华法林抗凝反应的影响。在给予W（1mg/kg，皮下注射）前24小时或同时，给大鼠腹腔注射溶解于玉米油中的S（6和12mmol/kg）或TCE（5.6和11.2mmol/kg）或CT（1mmol/kg），在给予W后24小时处死动物。本研究中使用的溶剂剂量显示出肝毒性作用，血清转氨酶反应显著增加证实了这一点。当W与任何剂量水平的S或TCE同时处理时，凝血酶原时间（P.T.）显著增加，但与CT同时处理时未出现这种情况。在预先用最高剂量的S或TCE处理的组以及CT组中，也观察到W的P.T.增加。单独的溶剂对P.T.没有影响。所以，急性接触有机溶剂可能会导致对华法林的抗凝反应增强。
