Effect of phenobarbital on hepatic eicosanoid concentrations in rats

被引:5
|
作者
Peebles, RS
Glauert, HP
机构
[1] UNIV KENTUCKY, DEPT NUTR & FOOD SCI, LEXINGTON, KY 40506 USA
[2] UNIV KENTUCKY, GRAD CTR TOXICOL, LEXINGTON, KY 40506 USA
关键词
phenobarbital; prostaglandin; leukotriene; hepatocarcinogenesis;
D O I
10.1007/s002040050439
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Phenobarbital is an efficacious tumor-promoting agent in the liver. Studies using inhibitors of eicosanoid synthesis have suggested that eicosanoids are important in the promotion of hepatocarcinogenesis by phenobarbital. We therefore hypothesized that hepatic eicosanoid concentrations are altered following phenobarbital administration. Male Sprague-Dawley rats were fed one of four levels of phenobarbital (0, 0.02, 0.05, and 0.1%). Eight rats from each of the four groups were killed after 10, 24, and 44 days for determination of liver weight and for preparation of microsomes, No significant difference was found among rat weights; however, liver weights were significantly higher in rats fed phenobarbital. Assay of benzyloxyresorufin-O-dealkylase activity showed that cytochromes P-450 2B1 and 2B2 were induced in response to phenobarbital administration. Prostaglandin E-2 concentrations were found to be significantly decreased by phenobarbital treatment after 10 and 24 days, but not after 44 days. Prostaglandin F-2 alpha levels were decreased only by the lowest dietary phenobarbital concentration. Hepatic concentrations of leukotriene C-4 were decreased significantly at 10 days and at 44 days (only for the group administered the highest percentage concentration of phenobarbital), but not at 24 days. These results show that the investigated eicosanoids are generally slightly decreased by phenobarbital administration. Elevated eicosanoid levels therefore do not appear to be necessary for the promoting activity of phenobarbital.
引用
收藏
页码:646 / 650
页数:5
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