Astorg P, Gradelet S, Leclerc J, Canivenc M C, Siess M H
Unité de Toxicologie Nutritionnelle, Institut National de la Recherche Agronomique, Dijon, France.
Food Chem Toxicol. 1994 Aug;32(8):735-42. doi: 10.1016/s0278-6915(09)80006-9.
The activities of several phase I and phase II xenobiotic-metabolizing enzymes have been measured in liver microsomes and cytosol of male rats that had been fed for 15 days with diets containing beta-carotene or canthaxanthin (300 mg/kg diet) or an excess of vitamin A (70,000 IU/kg diet), or to which beta-carotene had been administered by ip injections (7 x 10 mg/kg body weight). Microsomal cytochrome P-450 and the associated NADH- and NADPH-cytochrome c reductases were assayed, as well as several phase I and phase II enzyme activities. Phase I activities were markers of the families 1, 2, 3 and 4 of P-450; phase II activities were microsomal UDP glucuronosyl transferases (UGT) and cytosolic glutathione S-transferase (GST). Canthaxanthin accumulated in liver to a much higher level than did ingested or injected beta-carotene. Canthaxanthin increased the liver content of cytochrome P-450 (control value x 1.7), and the activity of NADH-cytochrome c reductase (x 1.5), and of some P-450-dependent enzymes (ethoxy-, methoxy-, pentoxy- and benzoxyresorufin O-dealkylases; x98, x15, x6.5 and x13, respectively), but not of others (erythromycin N-demethylase, nitrosodimethylamine N-demethylase and laurate omega-hydroxylase). Phase II activities were also increased: UGT1 (x3.4), UGT2 (x1.2) and GST (x1.2). This induction profile, characterized by the very strong increase of the activity associated with P4501A1, and the co-induction of UGT1, closely resemble that of a classical inducer, 3-methylcholanthrene. By contrast, neither beta-carotene (fed or injected), nor an excess of vitamin A induced any significant variation of the enzyme activities measured.
在雄性大鼠的肝脏微粒体和胞液中，测定了几种I相和II相异生物质代谢酶的活性。这些大鼠分别喂食含β-胡萝卜素或角黄素（300毫克/千克饲料）或过量维生素A（70,000国际单位/千克饲料）的饲料15天，或者通过腹腔注射给予β-胡萝卜素（7×10毫克/千克体重）。测定了微粒体细胞色素P-450以及相关的NADH-和NADPH-细胞色素c还原酶，以及几种I相和II相酶的活性。I相活性是P-450 1、2、3和4家族的标志物；II相活性是微粒体UDP葡糖醛酸基转移酶（UGT）和胞液谷胱甘肽S-转移酶（GST）。角黄素在肝脏中的蓄积水平比摄入或注射的β-胡萝卜素高得多。角黄素增加了细胞色素P-450的肝脏含量（对照值×1.7）、NADH-细胞色素c还原酶的活性（×1.5）以及一些P-450依赖性酶的活性（乙氧基、甲氧基、戊氧基和苯氧基试卤灵O-脱烷基酶；分别为×98、×15、×6.5和×13），但对其他酶（红霉素N-脱甲基酶、亚硝基二甲胺N-脱甲基酶和月桂酸ω-羟化酶）没有影响。II相活性也增加了：UGT1（×3.4）、UGT2（×1.2）和GST（×1.2）。这种诱导模式的特征是与P4501A1相关的活性大幅增加以及UGT1的共同诱导，与经典诱导剂3-甲基胆蒽非常相似。相比之下，无论是喂食还是注射的β-胡萝卜素，以及过量的维生素A，都未引起所测酶活性的任何显著变化。
