Dose-response effects of lycopene on selected drug-metabolizing and antioxidant enzymes in the rat.
Dose-response effects of lycopene on selected drug-metabolizing and antioxidant enzymes in the rat.
复制标题
DOI：
10.1016/s0304-3835(00)00401-8
复制
发表时间：
2000-06-30
期刊：
影响因子：
9.7
通讯作者：
Jakobsen, J
中科院分区：
文献类型：
--
作者：
Breinholt, V;Lauridsen, ST;Jakobsen, J
研究发现，每天给雌性大鼠服用番茄红素，剂量范围为 0.001 至 0.1 克/千克体重，持续两周，可改变暴露动物的药物代谢能力和抗氧化状态。对四种细胞色素 P450 依赖性酶的研究表明，在所有研究的番茄红素剂量下，肝脏中的苄氧基试卤灵 O-脱烷基酶活性均以剂量依赖性方式显着诱导。同样，乙氧基试卤灵O-脱烷基酶活性也被诱导，尽管仅在测试的两个最高番茄红素浓度下。对选定的第 2 阶段解毒酶的研究提供了证据，表明番茄红素能够在每天 0.001 至 0.05 g/kg 体重之间的剂量下诱导大约两倍的肝醌还原酶，而在其余测试剂量下没有观察到效果。使用两种底物 2,4-二氯硝基苯和 1-氯-2,4-二硝基苯，谷胱甘肽转移酶在 0.1 g/kg 体重下被显着诱导。每天剂量，而在剩余的番茄红素剂量下没有观察到效果。对血液室抗氧化状态的分析表明，四分之三的抗氧化酶受到番茄红素处理的影响。因此，在番茄红素剂量为0.005和0.05g/kg体重时，超氧化物歧化酶的活性被显着诱导，而谷胱甘肽还原酶和谷胱甘肽过氧化物酶仅在0.005g/kg体重时被诱导。每天剂量。对于所有研究的抗氧化酶，在 0.005 至 0.05 g/kg 体重之间的剂量下发挥峰值诱导后，活性似乎恢复到对照水平。每天。对此的解释仍然未知。饮食水平下番茄红素的血浆浓度为 0.001、0.005、0.05 和 0.1 g/kg b.w。据估计，每天的番茄红素浓度分别为 16、32、71 和 67 nM，勉强处于人类平均血浆番茄红素浓度（70-1790 nM）的较低范围内。杂环胺 2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶 (PhIP) 诱导的氧化应激，并通过分析血浆中的丙二醛进行了研究，未发现先前的影响。番茄红素暴露。肝脏或结肠中 PhIP-DNA 加合物的水平同样不受任何剂量的番茄红素的影响。总体而言，本研究提供的证据表明，在年轻雌性大鼠的饮食中添加番茄红素，对参与预防氧化应激和癌症的抗氧化剂和药物代谢酶具有轻微的改变作用。这些酶活性是在所有这些非常低的血浆水平下诱导的，这一事实可以表明抗氧化剂和药物代谢酶图谱的调节确实与人类相关，人类的血浆番茄红素水平通常比本研究中观察到的有效水平高出几倍。 (C) 2000 Elsevier Science Ireland Ltd. 保留所有权利。
The administration of lycopene to female rats at doses ranging from 0.001 to 0.1 g/kg b.w, per day for 2 weeks was found to alter the drug-metabolizing capacity and antioxidant status of the exposed animals. An investigation of four cytochrome P450-dependent enzymes revealed that benzyloxyresorufin O-dealkylase activity in the liver was significantly induced in a dose-dependent fashion at all lycopene doses investigated. Likewise, ethoxyresorufin O-dealkylase activity was induced, although only at the two highest lycopene concentrations tested. An investigation of selected phase 2 detoxification enzymes provided evidence that lycopene was capable of inducing hepatic quinone reductase, approximately two-fold, at doses between 0.001 and 0.05 g/kg b.w, per day, whereas no effect was observed at the remaining doses tested. Glutathione transferase, using the two substrates, 2,4-dichloronitrobenzene and 1-chloro-2,4-dinitrobenzene, was significantly induced at the 0.1 g/kg b.w. per day dose, whereas no effect was observed at the remaining lycopene doses. Analysis of the antioxidant status of thr blood compartment revealed that three out of four antioxidant enzymes were affected by lycopene treatment. The activity of superoxide dismutase was thus significantly induced at lycopene doses of 0.005 and 0.05 g/kg b.w, whereas glutathione reductase and glutathione peroxidase was only induced at the 0.005 g/kg b.w. per day dose. For all antioxidant enzymes investigated, the activities seemed to return to the control level after exerting peak induction at doses between 0.005 and 0.05 g/kg b.w. per day. The explanation for this remains unknown. The plasma concentration of lycopene at dietary levels of 0.001, 0.005, 0.05 and 0.1 g/kg b.w. per day was estimated to be 16, 32, 71 and 67 nM, which is barely within the lower range of the mean human plasma concentration of lycopene, which ranges from 70-1790 nM. Oxidative stress induced by the heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), and investigated by analyzing for malondialdehyde in plasma, was not found to be affected by prior. lycopene exposure. The level of PhIP-DNA adducts in the liver or colon was likewise not affected by lycopene at any dose. Overall, the present study provides evidence that lycopene administered in the diet of young female rats exerts minor modifying effects toward antioxidant and drug-metabolizing enzymes involved in the protection against oxidative stress and cancer. The fact that these enzymatic activities are induced at all of these very low plasma levels, could be taken to suggest that modulation of antioxidant and drug-metabolizing enzymes map indeed be relevant to humans, which in general exhibit a plasma lycopene level several fold above the effective levels observed in this study. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.