Vang O, Frandsen H, Hansen K T, Nielsen J B, Andersen O
Department of Life Sciences and Chemistry, Roskilde University, Denmark.
Pharmacol Toxicol. 1999 Feb;84(2):59-65. doi: 10.1111/j.1600-0773.1999.tb00875.x.
Indole-3-ylcarbinol (13C) is formed during processing of cruciferous vegetables and is suggested to be one of the modulators of drug-metabolising enzymes. Indole-3-ylcarbinol is a far less efficient inducer of hepatic enzymes after parenteral than after oral administration, due to formation of active metabolites in the gastrointestinal tract. As indole-3-ylcarbinol is unstable in weakly acidic aqueous solutions, non-active condensation products may be formed from indole-3-ylcarbinol, that cannot be transformed to the active products when reaching the stomach. The purpose of the present study was to test the ability of the condensation products formed at a pH corresponding to that of fresh vegetable juice to modulate the metabolism of xenobiotics. Indole-3-ylcarbinol was incubated in vitro at room temperature in the dark at pH 5.5 and samples taken at various times, for oral administration to rats and for chemical analysis. Indole-3-ylcarbinol was rapidly transformed into various oligomeric products. The 7-ethoxyresorufin O-deethylase activities (marker of cytochrome Cytochrome P450 1A enzymes, CYP1A) in liver, kidney and colon increased with the duration of the in vitro condensation period whereas the formation of 6beta-, 15beta- and and 2alpha-hydroxytestosterone was not affected significantly, indicating no effect on CYP2C11 or CYP3A enzymes. The hepatic metabolism of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). was increased by indole-3-ylcarbinol condensation products and the 4'-OH-PhIP/N-OH-PhIP ratio was decreased due to a significantly increased formation of the proximate genotoxic metabolite. N-OH-PhIP. The activities of DT-diaphorase and glutathione S-transferase were not changed significantly in the rat organs. These experiments clearly indicate that indole-3-ylcarbinol is not the definitive CYP1A inducer and that indole-3-ylcarbinol at near-neutral pH, is transformed to compounds that are inducers by themselves or may be further converted into inducing compounds in the rat stomach. Also, the enzyme inducing potency of indole-3-ylcarbinol containing vegetable juice is apparently enhanced by incubation in vitro before the intake.
吲哚 - 3 - 甲醇（13C）在十字花科蔬菜加工过程中形成，被认为是药物代谢酶的调节剂之一。与口服给药相比，吲哚 - 3 - 甲醇经肠胃外给药后对肝酶的诱导效率要低得多，这是因为在胃肠道中会形成活性代谢产物。由于吲哚 - 3 - 甲醇在弱酸性水溶液中不稳定，可能会形成非活性缩合产物，这些产物在进入胃部时无法转化为活性产物。本研究的目的是测试在与新鲜蔬菜汁pH值相当的条件下形成的缩合产物调节外源性物质代谢的能力。将吲哚 - 3 - 甲醇在室温、黑暗条件下于pH 5.5体外孵育，在不同时间取样，用于给大鼠口服及化学分析。吲哚 - 3 - 甲醇迅速转化为各种寡聚产物。肝脏、肾脏和结肠中的7 - 乙氧基异吩恶唑酮 - O - 脱乙基酶活性（细胞色素细胞色素P450 1A酶，CYP1A的标志物）随着体外缩合时间的延长而增加，而6β -、15β - 和2α - 羟基睾酮的形成未受到显著影响，表明对CYP2C11或CYP3A酶无作用。食物诱变剂2 - 氨基 - 1 - 甲基 - 6 - 苯基咪唑并[4,5 - b]吡啶（PhIP）的肝脏代谢因吲哚 - 3 - 甲醇缩合产物而增加，并且由于近端遗传毒性代谢产物N - OH - PhIP的形成显著增加，4'-OH - PhIP/N - OH - PhIP比值降低。大鼠器官中的DT - 黄递酶和谷胱甘肽S - 转移酶活性未发生显著变化。这些实验清楚地表明，吲哚 - 3 - 甲醇不是确定的CYP1A诱导剂，并且在接近中性pH值时，吲哚 - 3 - 甲醇会转化为自身就是诱导剂的化合物，或者可能在大鼠胃中进一步转化为诱导性化合物。此外，含有吲哚 - 3 - 甲醇的蔬菜汁在摄入前通过体外孵育，其酶诱导效力明显增强。
