Interdisciplinary Faculty of Toxicology, Texas A&M University, College Station, TX 77843, USA.
Department of Environmental & Occupational Health, Texas A&M University, College Station, TX 77843, USA.
Toxicol Appl Pharmacol. 2024 Jan;482:116796. doi: 10.1016/j.taap.2023.116796. Epub 2023 Dec 23.
Sulforaphane (SFN) is a bioactive phytonutrient found in cruciferous vegetables. There is a lack of detailed information on the lactational transfer of SFN and SFN metabolites, and potential pharmacological effects on breastfeeding infants. We carried out two maternal supplementation studies in a mouse model, wherein lactating dams received either vehicle, 300 or 600 ppm SFN from postnatal day (PND) 1 to 5, or in a second experiment, vehicle or 600 ppm SFN from PND 1 to 14. The parent compound was only detectable in milk and plasma from dams receiving 600 ppm SFN for five days. The predominant metabolite SFN-N-acetylcysteine (SFN-NAC) was readily detected in milk from dams receiving 300 and 600 ppm SFN for five days or 600 ppm for 14 days. Maternal SFN-NAC plasma levels were elevated in both 600 ppm groups. Maternal hepatic and pulmonary expression of NRF2-related genes, Nqo1, Gsta2, Gstm1, and Gstp1, were significantly increased, generally following a dose-response; however, offspring induction varied. PND5 neonates in the 600-ppm group exhibited significantly elevated expression of Nqo1, Gsta2, and Gstp1 in liver, and Gstm1 and Gstp1 in lung. Findings support maternal dietary supplementation with SFN induces NRF2-related gene expression in neonates via lactational transfer of SFN-NAC. However, NQO1 enzyme activity was not significantly elevated, highlighting the need to optimize dosing strategy. Additionally, in a pilot investigation of lactating women consuming a typical diet, without any purified SFN supplementation, 7 out of 8 breast milk samples showed SFN-NAC above the limit of quantification (LOQ). Notably, the one sample below the LOQ was collected from the only participant who reported no consumption of cruciferous vegetables in the past 24 h. The parent compound was not detected in any of the human breast milk samples. Overall, these data indicate lactational transfer of SFN-NAC at dietary relevant levels. Future studies are needed to evaluate pharmacokinetics and pharmacodynamics of lactational transfer for potential preventive or therapeutic effects in breastfeeding children.
萝卜硫素（SFN）是十字花科蔬菜中发现的一种生物活性植物营养素。关于 SFN 和 SFN 代谢物的哺乳期转移以及对母乳喂养婴儿的潜在药理作用，缺乏详细信息。我们在小鼠模型中进行了两项母体补充研究，其中哺乳期母鼠在产后第 1 天至第 5 天接受载体、300 或 600ppm SFN，或者在第二个实验中，在产后第 1 天至第 14 天接受载体或 600ppm SFN。母体化合物仅在接受 600ppm SFN 五天的母鼠的乳汁和血浆中可检测到。主要代谢物 SFN-N-乙酰半胱氨酸（SFN-NAC）在接受 300 和 600ppm SFN 五天或 600ppm SFN 14 天的母鼠的乳汁中很容易检测到。母体 SFN-NAC 血浆水平在 600ppm 两组均升高。母体肝和肺中 NRF2 相关基因 Nqo1、Gsta2、Gstm1 和 Gstp1 的表达显著增加，通常呈剂量反应；然而，后代的诱导则不同。在 600ppm 组中，PND5 新生儿的肝中 Nqo1、Gsta2 和 Gstp1 以及肺中的 Gstm1 和 Gstp1 的表达显著升高。研究结果支持通过 SFN-NAC 的哺乳期转移，母体膳食补充 SFN 可诱导新生儿的 NRF2 相关基因表达。然而，NQO1 酶活性并未显著升高，这突出表明需要优化给药策略。此外，在一项对食用典型饮食的哺乳期妇女的初步调查中，在没有任何纯化 SFN 补充的情况下，8 份母乳样本中有 7 份 SFN-NAC 的含量超过定量限（LOQ）。值得注意的是，唯一一份低于 LOQ 的样本是从唯一一位在过去 24 小时内报告未食用十字花科蔬菜的参与者中收集的。在任何人类母乳样本中均未检测到母体化合物。总体而言，这些数据表明 SFN-NAC 以饮食相关水平进行哺乳期转移。需要进一步的研究来评估哺乳期转移的药代动力学和药效学，以评估其对母乳喂养儿童的潜在预防或治疗作用。
