Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, 50005 Hradec Králové, Czech Republic.
Molecules. 2017 Nov 16;22(11):1983. doi: 10.3390/molecules22111983.
Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, exerts many beneficial effects on human health such as antioxidant, anti-inflammatory, and anticancer effects. The effect of SFN alone on drug-metabolizing enzymes (DMEs) has been investigated in numerous in vitro and in vivo models, but little is known about the effect of SFN in combination with cytochrome P450 (CYP) inducer. The aim of our study was to evaluate the effect of SFN on the activity and gene expression of selected DMEs in primary cultures of rat hepatocytes treated or non-treated with β-naphthoflavone (BNF), the model CYP1A inducer. In our study, SFN alone did not significantly alter the activity and expression of the studied DMEs, except for the glutathione S-transferase (GSTA1) mRNA level, which was significantly enhanced. Co-treatment of hepatocytes with SFN and BNF led to a substantial increase in sulfotransferase, aldoketoreductase 1C, carbonylreductase 1 and NAD(P)H:quinone oxidoreductase 1 activity and a marked decrease in cytochrome P450 (CYP) , and expression in comparison to the treatment with BNF alone. Sulforaphane is able to modulate the activity and/or expression of DMEs, thus shifting the balance of carcinogen metabolism toward deactivation, which could represent an important mechanism of its chemopreventive activity.
萝卜硫素（SFN）是十字花科蔬菜中发现的一种异硫氰酸盐，对人类健康具有许多有益的影响，如抗氧化、抗炎和抗癌作用。SFN 对药物代谢酶（DMEs）的单独作用已在许多体外和体内模型中进行了研究，但对于 SFN 与细胞色素 P450（CYP）诱导剂联合使用的效果知之甚少。我们的研究目的是评估 SFN 对用β-萘黄酮（BNF）处理或未处理的大鼠肝细胞原代培养物中选定的 DME 活性和基因表达的影响，BNF 是 CYP1A 诱导剂的模型。在我们的研究中，SFN 单独处理不会显著改变研究 DME 的活性和表达，除了谷胱甘肽 S-转移酶（GSTA1）mRNA 水平显著增强。与 BNF 单独处理相比，SFN 和 BNF 共同处理肝细胞导致磺基转移酶、醛酮还原酶 1C、羰基还原酶 1 和 NAD(P)H：醌氧化还原酶 1 的活性显著增加，细胞色素 P450（CYP）和表达显著降低。SFN 能够调节 DME 的活性和/或表达，从而使致癌物代谢的平衡向失活方向转移，这可能是其化学预防活性的重要机制。
