Seidegård J, DePierre J W, Morgenstern R, Pilotti A, Ernster L
Biochim Biophys Acta. 1981 Jan 7;672(1):65-78. doi: 10.1016/0304-4165(81)90280-4.
trans-Stilbene oxide has been found to be a new type of inducer of drug-metabolizing systems. In order to identify the true inducer and to determine the structural requirements for induction, rats were treated with metabolites and structural analogues of stilbene. Subsequently, hepatic levels of cytochrome P-450, microsomal epoxide hydrolase, and cytoplasmic glutathione S-transferase were assayed. All three enzymes were induced by cis- and trans-stilbene and cis- and trans-stilbene oxide. In addition, epoxide hydrolase and glutathione S-transferase activities were induced by benzoin and benzil. In contrast, the diols and benzoic acid had little, if any, effect. The main conclusions drawn from these findings are that: (1) trans-stilbene oxide itself seems to be the inducer of drug-metabolizing enzymes; and (2) benzil is more selective as an inducer of epoxide hydrolase than is trans-stilbene oxide. Attempts to induce epoxide hydrolase with other structural analogues of stilbene led to the following conclusions: (1) two phenyl rings are required for induction; (2) the induction is not as great if the rings are substituted or one of the ring carbon atoms is replaced by a nitrogen; (3) a carbon bridge between the phenyl groups generally results in a greater induction, especially if the bridge contains an epoxy group or one or two keto groups.
反式氧化芪已被发现是一种新型的药物代谢系统诱导剂。为了确定真正的诱导剂并确定诱导的结构要求，用芪的代谢产物和结构类似物处理大鼠。随后，测定细胞色素P - 450、微粒体环氧化物水解酶和细胞质谷胱甘肽S - 转移酶的肝脏水平。所有这三种酶都被顺式和反式芪以及顺式和反式氧化芪诱导。此外，苯偶姻和苯偶酰诱导了环氧化物水解酶和谷胱甘肽S - 转移酶的活性。相比之下，二醇和苯甲酸几乎没有影响。从这些发现得出的主要结论是：(1)反式氧化芪本身似乎是药物代谢酶的诱导剂；(2)苯偶酰作为环氧化物水解酶的诱导剂比反式氧化芪更具选择性。用芪的其他结构类似物诱导环氧化物水解酶的尝试得出了以下结论：(1)诱导需要两个苯环；(2)如果环被取代或其中一个环碳原子被氮取代，诱导作用就不会那么大；(3)苯环之间的碳桥通常会导致更大的诱导作用，特别是如果桥中含有环氧基或一个或两个酮基。
