Condie L W, Laurie R D, Mills T, Robinson M, Bercz J P
Fundam Appl Toxicol. 1986 Aug;7(2):199-206. doi: 10.1016/0272-0590(86)90148-x.
This investigation was conducted to evaluate the effect of gavage vehicles on altering the severity of the subchronic hepatotoxicity of carbon tetrachloride (CCl4). Male and female CD-1 mice were gavaged with 0, 1.2, 12, and 120 mg/kg CCl4 in either a corn oil or 1% Tween-60 vehicle once daily for 5 consecutive days per week for 90 days. The study revealed that the hepatotoxicity was greater in the mid- and high-dose groups of mice that had received CCl4 administered in corn oil. Increases in serum enzyme activities were detected in the mid-dose groups of mice that were gavaged with CCl4 in corn oil. The serum enzyme activities were significantly higher in the high-dose groups of animals in which CCl4 was administered in corn oil. Histopathological findings indicated that hepatocellular changes following the administration of CCl4 at the mid- and high-dose levels were more frequent and more severe when CCl4 was given in corn oil than when it was administered in Tween-60. The experimental findings indicate that the no-observed-adverse-effect level from CCl4 exposure was lowered by an order of magnitude (from 12 to 1.2 mg/kg) and that the hepatotoxicity of CCl4 was enhanced in the high-dose treatment groups when corn oil was employed as the gavage vehicle.
本研究旨在评估灌胃溶媒对改变四氯化碳(CCl4)亚慢性肝毒性严重程度的影响。将雄性和雌性CD-1小鼠每周连续5天每天一次用玉米油或1%吐温-60溶媒灌胃给予0、1.2、12和120 mg/kg CCl4,持续90天。研究显示,接受玉米油中给予CCl4的小鼠中、高剂量组的肝毒性更大。在玉米油中灌胃给予CCl4的小鼠中剂量组检测到血清酶活性增加。在玉米油中给予CCl4的动物高剂量组中血清酶活性显著更高。组织病理学结果表明,中、高剂量水平给予CCl4后,与吐温-60中给予CCl4相比,玉米油中给予CCl4时肝细胞变化更频繁且更严重。实验结果表明,CCl4暴露的未观察到不良反应水平降低了一个数量级(从12降至1.2 mg/kg),并且当使用玉米油作为灌胃溶媒时,CCl4在高剂量治疗组中的肝毒性增强。