Thakore K N, Mehendale H M
Division of Pharmacology and Toxicology, College of Pharmacy and Health Sciences, Northeast Louisiana University, Monroe 71209-0470.
Toxicol Pathol. 1994 May-Jun;22(3):291-9. doi: 10.1177/019262339402200307.
Male Sprague-Dawley rats maintained on either normal diet (N) or on a diet containing phenobarbital (PB; 225 ppm) or mirex (M; 10 ppm) for 15 days received either corn oil or 1 single administration of a protective dose of CCl4 (0.3 ml/kg, po) on day 16. At 24, 48, 72, 96, or 144 hr after the protective dose, a high dose of CCl4 (5 ml/kg, po) was administered to rats of all the groups, and they were observed for 14-day lethality. In a second experiment, in rats maintained on N, PB, or M diet, liver microsomal cytochromes P-450, aminopyrine demethylase, and aniline hydroxylase were measured at various time points after the administration of the protective dose of CCl4. Serum aspartate transaminase, alanine transaminase, and sorbitol dehydrogenase elevations and histopathological changes observed under a light microscope were used as toxic end points to assess hepatotoxicity. Autoprotection was 100% when the high dose was given at 24 hr after the protective dose in N rats, whereas it was only 55% in PB- or M-pretreated rats. For later time points of 48, 72, and 96 hr, autoprotection was only around 50% in N rats, whereas it was almost 100% in PB- and M-pretreated rats. When the high dose was administered at 144 hr after the protective dose, autoprotection further declined to 25% in N rats and to 75% in M-treated rats, but it remained at 100% in PB-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
将雄性斯普拉格-道利大鼠分为三组，分别给予正常饮食（N）、含苯巴比妥（PB；225 ppm）的饮食或含灭蚁灵（M；10 ppm）的饮食，持续15天。在第16天，所有组的大鼠均接受玉米油或单次给予保护剂量的四氯化碳（0.3 ml/kg，口服）。在给予保护剂量后的24、48、72、96或144小时，对所有组的大鼠给予高剂量的四氯化碳（5 ml/kg，口服），并观察其14天的致死率。在第二个实验中，对给予N、PB或M饮食的大鼠，在给予保护剂量的四氯化碳后的不同时间点测量肝脏微粒体细胞色素P-450、氨基比林脱甲基酶和苯胺羟化酶。血清天冬氨酸转氨酶、丙氨酸转氨酶和山梨醇脱氢酶的升高以及光镜下观察到的组织病理学变化被用作评估肝毒性的毒性终点。当在给予保护剂量后24小时给予高剂量时，N组大鼠的自身保护率为100%，而PB或M预处理组大鼠的自身保护率仅为55%。对于48、72和96小时的较晚时间点，N组大鼠的自身保护率仅约为50%，而PB和M预处理组大鼠的自身保护率几乎为100%。当在给予保护剂量后144小时给予高剂量时，N组大鼠的自身保护率进一步降至25%，M处理组大鼠降至75%，但PB处理组大鼠仍保持在100%。（摘要截断于250字）
