Bortolato Silvia, Zanovello Alberta, Rugge Massimo, Brotto Maurizio, Marini Sandra, Gervasi Pier Giovanni, Manno Maurizio
Department of Environmental Medicine and Public Health, University of Padua, Via Giustiniani 2, 35128 Padova, Italy.
Toxicol Lett. 2003 Sep 15;144(1):35-47. doi: 10.1016/s0378-4274(03)00228-5.
Trifluoroacetylated (TFA)-protein adducts were investigated by immunoblotting in liver and plasma of guinea pigs treated with the hepatotoxic anaesthetic halothane or the chlorofluorocarbon replacement 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123). Male outbred Hartley guinea pigs (320-400 g) were administered HCFC-123 (1, 5, 10 and 15 mmol/kg b.w.) or halothane (positive control, 10 mmol/kg b.w.) i.p. in corn oil. Blood and liver samples were collected 24 h after administration of HCFC-123 or halothane. Immunoreactive bands were demonstrated in liver microsomes at all HCFC-123 and halothane concentrations, and in plasma of animals treated with 10 and 15 mmol/kg b.w. HCFC-123 and 10 mmol/kg b.w. halothane, while no alteration of microsomal P450 content or monooxygenase activities markers of the P450 2A, 2E1 and 2B isoforms was observed. Instead, when HCFC-123 was administered at doses of 1 and 5 mmol/kg b.w., the 2E1-dependent p-nitrophenol hydroxylase activity was enhanced. The presence of TFA-proteins in plasma was always associated with hepatic damage. However, mild liver damage in some animals treated with 1 or 5 mmol/kg b.w. HCFC-123 was not associated with the presence of TFA-proteins in plasma. This indicates a lower threshold dose for the appearance of TFA-proteins or damage in the liver (1 mmol/kg b.w.) than for the presence of TFA-proteins in plasma (10 mmol/kg b.w.), thus suggesting that the presence of TFA-proteins in plasma may be the result of liver damage.
通过免疫印迹法，对用具有肝毒性的麻醉剂氟烷或氯氟烃替代品1,1 - 二氯 - 2,2,2 - 三氟乙烷（HCFC - 123）处理的豚鼠肝脏和血浆中的三氟乙酰化（TFA）蛋白加合物进行了研究。将雄性远交系Hartley豚鼠（320 - 400克）腹腔注射HCFC - 123（1、5、10和15毫摩尔/千克体重）或氟烷（阳性对照，10毫摩尔/千克体重），溶剂为玉米油。在注射HCFC - 123或氟烷24小时后采集血液和肝脏样本。在所有HCFC - 123和氟烷浓度下，肝脏微粒体中均出现免疫反应条带，在用10和15毫摩尔/千克体重HCFC - 123以及10毫摩尔/千克体重氟烷处理的动物血浆中也出现免疫反应条带，而未观察到微粒体P450含量或P450 2A、2E1和2B同工型的单加氧酶活性标志物有改变。相反，当以1和5毫摩尔/千克体重的剂量给予HCFC - 123时，依赖2E1的对硝基苯酚羟化酶活性增强。血浆中TFA蛋白的存在总是与肝损伤相关。然而，一些用1或5毫摩尔/千克体重HCFC - 123处理的动物出现的轻度肝损伤与血浆中TFA蛋白的存在无关。这表明肝脏中TFA蛋白出现或损伤的阈值剂量（1毫摩尔/千克体重）低于血浆中TFA蛋白存在的阈值剂量（10毫摩尔/千克体重），因此表明血浆中TFA蛋白的存在可能是肝损伤的结果。
