Thompson D C, Trush M A
Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205.
Toxicol Appl Pharmacol. 1988 Oct;96(1):115-21. doi: 10.1016/0041-008x(88)90253-0.
The phenolic antioxidant butylated hydroxytoluene (BHT) is known to produce a dose-dependent increase in mouse lung weight which is characterized by the necrosis of pulmonary type I and endothelial cells. We studied the ability of butylated hydroxyanisole (BHA) to modify BHT-induced changes in lung weight in male CD-1 mice. BHA alone had no effect on lung weight up to a dose of 500 mg/kg (sc). However, when injected 30 minutes prior to sub-threshold doses of BHT (0-250 mg/kg, ip), BHA significantly enhanced lung weight in a dose-dependent manner. The ability of BHA to enhance BHT-induced changes in lung weight was dependent on both the time and the route of administration of BHA relative to BHT. Deuteration of BHT abolished the in vivo toxicity from the combination of BHA and BHT. These results suggest that the toxicity resulting from the combination of BHA and BHT is due to the formation of BHT-quinone methide and that the role of BHA might be either to deplete some protective mechanism in the target pulmonary cells or to enhance the biotransformation of BHT into BHT-quinone methide.
已知酚类抗氧化剂丁基羟基甲苯（BHT）会使小鼠肺重量呈剂量依赖性增加，其特征为肺I型细胞和内皮细胞坏死。我们研究了丁基羟基茴香醚（BHA）改变BHT诱导的雄性CD-1小鼠肺重量变化的能力。单独使用BHA，剂量高达500 mg/kg（皮下注射）时对肺重量无影响。然而，在低于阈值剂量的BHT（0 - 250 mg/kg，腹腔注射）前30分钟注射BHA时，BHA会以剂量依赖性方式显著增加肺重量。BHA增强BHT诱导的肺重量变化的能力取决于BHA相对于BHT的给药时间和途径。BHT的氘代消除了BHA和BHT联合使用时的体内毒性。这些结果表明，BHA和BHT联合使用产生的毒性是由于BHT-醌甲基化物的形成，并且BHA的作用可能是耗尽靶肺细胞中的某些保护机制，或者增强BHT向BHT-醌甲基化物的生物转化。
