Effect of phenobarbital on hepatic eicosanoid concentrations in rats.
Effect of phenobarbital on hepatic eicosanoid concentrations in rats.
复制标题
苯巴比妥对大鼠肝脏类二十烷酸浓度的影响。
DOI：
10.1007/s002040050439
复制
发表时间：
1997
影响因子：
6.1
通讯作者：
Glauert,HP
中科院分区：
文献类型：
--
作者：
Peebles,RS;Glauert,HP
苯巴比妥是一种有效的肝脏肿瘤促进剂。使用类花生酸合成抑制剂的研究表明，类花生酸在苯巴比妥促进肝癌发生中很重要。因此，我们假设苯巴比妥给药后肝脏类花生酸浓度发生改变。雄性Sprague-Dawley大鼠喂食四种水平（0、0.02、0.05和0.1%）的苯巴比妥。分别在10、24和44天后处死4组中每组8只大鼠，以测定肝脏重量并制备微粒体。未发现大鼠体重之间存在显著差异;然而，喂食苯巴比妥的大鼠肝脏重量显著较高。苄氧基试卤灵-O-脱烷基酶活性测定表明，细胞色素P-450 2B 1和2B 2诱导响应苯巴比妥管理。发现苯巴比妥治疗10天和24天后前列腺素E2浓度显着下降，但44天后则没有下降。前列腺素F2α水平仅通过最低饮食苯巴比妥浓度降低。在第10天和第44天（仅给予最高百分比浓度苯巴比妥的组），肝脏中白三烯C4浓度显著降低，但在第24天未降低。这些结果表明，苯巴比妥给药后，研究的类二十烷酸通常略有减少。因此，类花生酸水平升高似乎不是促进苯巴比妥活性所必需的。
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 E2concentrations were found to be significantly decreased by phenobarbital treatment after 10 and 24 days, but not after 44 days. Prostaglandin F2αlevels were decreased only by the lowest dietary phenobarbital concentration. Hepatic concentrations of leukotriene C4were 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.