Potentiation of vitamin A hepatotoxicity by butylated hydroxytoluene.
Potentiation of vitamin A hepatotoxicity by butylated hydroxytoluene.
复制标题
丁基羟基甲苯增强维生素 A 的肝毒性。
DOI：
10.1016/0041-008x(87)90300-0
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发表时间：
1987
影响因子：
3.8
通讯作者：
Detrisac,CJ
中科院分区：
文献类型：
--
作者：
McCormick,DL;Hultin,TA;Detrisac,CJ
研究了天然维生素A酯醋酸视黄酯（RA）与酚类抗氧化剂丁基羟基甲苯（BHT）在诱导雌性Sprague-Dawley大鼠胆道增生和肝纤维化中的相互作用。采用3 × 3基质设计，在饲粮中添加（每千克饲粮）0、125或250 mg RA和/或0、2500或5000 mg BHT。125 mg剂量的RA未引起严重肝毒性，而250 mg剂量的RA在暴露120天和180天后检查的大鼠中引起低发生率的肝纤维化。单独暴露于BHT诱导肝细胞肥大和剂量相关的肝重量增加，但没有肝细胞病理。与单独使用RA相比，同时使用RA和BHT导致胆道增生和肝纤维化的发生率显著增加。BHT降低了所有RA剂量水平下肝脏总维生素A含量。因此，除了肝脏维生素A水平的增加之外，BHT增强RA肝毒性的机制必须是潜在的。
The interaction between the natural vitamin A ester retinyl acetate (RA) and the phenolic antioxidant butylated hydroxytoluene (BHT) in the induction of biliary hyperplasia and hepatic fibrosis in female Sprague-Dawley rats was characterized. Using a 3 × 3 matrix design, rats were fed diets supplemented with (per kilogram diet) 0, 125, or 250 mg RA and/or 0, 2500, or 5000 mg BHT. The 125-mg dose of RA induced no gross hepatotoxicity, while the 250-mg dose of RA induced a low incidence of hepatic fibrosis in rats examined after 120 and 180 days of exposure. Exposure to BHT alone induced hepatocellular hypertrophy and dose-related increases in liver weight, but no hepatocellular pathology. Simultaneous administration of RA plus BHT resulted in significant increases in the incidence of biliary hyperplasia and hepatic fibrosis compared to that induced by RA alone. BHT reduced total hepatic vitamin A content at all RA dose levels. Thus, mechanisms other than increases in liver vitamin A levels must underlie the potentiation by BHT of RA hepatotoxicity.