Molecular and Cellular Biology Program, Oregon State University, Corvallis, Oregon 97331, USA.
Pharm Res. 2011 Dec;28(12):3171-9. doi: 10.1007/s11095-011-0500-z. Epub 2011 Jun 17.
To determine the metabolism and tissue distribution of the dietary chemoprotective agent sulforaphane following oral administration to wild-type and Nrf2 knockout (Nrf2(-/-)) mice.
Male and female wild-type and Nrf2(-/-) mice were given sulforaphane (5 or 20 μmoles) by oral gavage; plasma, liver, kidney, small intestine, colon, lung, brain and prostate were collected at 2, 6 and 24 h (h). The five major metabolites of sulforaphane were measured in tissues by high performance liquid chromatography coupled with tandem mass spectrometry.
Sulforaphane metabolites were detected in all tissues at 2 and 6 h post gavage, with the highest concentrations in the small intestine, prostate, kidney and lung. A dose-dependent increase in sulforaphane concentrations was observed in all tissues except prostate. At 5 μmole, Nrf2(-/-) genotype had no effect on sulforaphane metabolism. Only Nrf2(-/-) females given 20 μmoles sulforaphane for 6 h exhibited a marked increase in tissue sulforaphane metabolite concentrations. The relative abundance of each metabolite was not strikingly different between genders and genotypes.
Sulforaphane is metabolized and reaches target tissues in wild-type and Nrf2(-/-) mice. These data provide further evidence that sulforaphane is bioavailable and may be an effective dietary chemoprevention agent for several tissue sites.
确定膳食化学保护剂萝卜硫素经口服给药后在野生型和 Nrf2 敲除（Nrf2(-/-)）小鼠体内的代谢和组织分布。
雄性和雌性野生型和 Nrf2(-/-)小鼠经口服灌胃给予萝卜硫素（5 或 20 μmol）；在 2、6 和 24 小时（h）时收集血浆、肝脏、肾脏、小肠、结肠、肺、脑和前列腺。通过高效液相色谱-串联质谱法测定组织中萝卜硫素的 5 种主要代谢物。
在灌胃后 2 和 6 小时，所有组织中均检测到萝卜硫素代谢物，在小肠、前列腺、肾脏和肺中的浓度最高。除前列腺外，所有组织中的萝卜硫素浓度均呈剂量依赖性增加。在 5 μmol 时，Nrf2(-/-)基因型对萝卜硫素代谢没有影响。只有接受 20 μmol 萝卜硫素 6 小时的 Nrf2(-/-)雌性小鼠显示组织萝卜硫素代谢物浓度显著增加。各代谢物的相对丰度在性别和基因型之间没有明显差异。
萝卜硫素在野生型和 Nrf2(-/-)小鼠中被代谢并到达靶组织。这些数据进一步证明萝卜硫素是生物可利用的，并且可能是几种组织部位的有效膳食化学预防剂。
