水中污染物的相互作用。I. 大鼠经口灌胃单独及联合给予四氯化碳、氯仿或三氯乙烯后血浆酶活性及响应面法研究

Interactions of water contaminants. I. Plasma enzyme activity and response surface methodology following gavage administration of CCl4 and CHCl3 or TCE singly and in combination in the rat.

作者信息

Borzelleca J F, O'Hara T M, Gennings C, Granger R H, Sheppard M A, Condie L W

机构信息

Department of Pharmacology, Medical College of Virginia, Richmond 23298.

出版信息

Fundam Appl Toxicol. 1990 Apr;14(3):477-90. doi: 10.1016/0272-0590(90)90252-f.

DOI:10.1016/0272-0590(90)90252-f

PMID:2340978

Abstract

The joint hepatotoxicity of CCl4 and CHCl3 or TCE in male CD rats following simultaneous oral administration has been investigated. Rats with chronic indwelling arterial cannulas were administered a single oral dose of CCl4 and CHCl3 or CCl4 and TCE in 5% Emulphor at doses of 0 to 700 mg/kg. Hepatotoxicity was evaluated by measuring the activity of AST, ALT, and SDH in plasma at 0, 3, 6, 12, 24, 36, 48, and 72 hr postgavage. Response data were analyzed for interaction using response surface methodology. CCl4 alone displayed dose-dependent toxicity. TCE demonstrated little evidence of hepatotoxicity. In combination, both CCl4/CHCl3 and CCl4/TCE displayed a synergistic (supraadditive) response for peak plasma enzyme activity.

摘要

研究了雄性CD大鼠同时口服四氯化碳（CCl4）与三氯甲烷（CHCl3）或三氯乙烯（TCE）后的联合肝毒性。给慢性留置动脉插管的大鼠经口单次给予0至700mg/kg剂量的CCl4与CHCl3或CCl4与TCE的5%聚氧乙烯蓖麻油溶液。在灌胃后0、3、6、12、24、36、48和72小时，通过测量血浆中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和山梨醇脱氢酶（SDH）的活性来评估肝毒性。使用响应面法分析反应数据的相互作用。单独的CCl4表现出剂量依赖性毒性。TCE几乎没有肝毒性证据。CCl4/CHCl3和CCl4/TCE联合使用时，血浆酶活性峰值均表现出协同（超相加）反应。