Riedl Marc A, Saxon Andrew, Diaz-Sanchez David
The Hart and Louis Laboratory, Clinical Immunology and Allergy, Department of Medicine, UCLA David Geffen School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Clin Immunol. 2009 Mar;130(3):244-51. doi: 10.1016/j.clim.2008.10.007. Epub 2008 Nov 22.
Cellular oxidative stress is an important factor in asthma and is thought to be the principle mechanism by which oxidant pollutants such as ozone and particulates mediate their pro-inflammatory effects. Endogenous Phase II enzymes abrogate oxidative stress through the scavenging of reactive oxygen species and metabolism of reactive chemicals.
We conducted a placebo-controlled dose escalation trial to investigate the in vivo effects of sulforaphane, a naturally occurring potent inducer of Phase II enzymes, on the expression of glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1) in the upper airway of human subjects.
Study subjects consumed oral sulforaphane doses contained in a standardized broccoli sprout homogenate (BSH). RNA expression for selected Phase II enzymes was measured in nasal lavage cells by RT-PCR before and after sulforaphane dosing.
All subjects tolerated oral sulforaphane dosing without significant adverse events. Increased Phase II enzyme expression in nasal lavage cells occurred in a dose-dependent manner with maximal enzyme induction observed at the highest dose of 200 g broccoli sprouts prepared as BSH. Significant increases were seen in all sentinel Phase II enzymes RNA expression compared to baseline. Phase II enzyme induction was not seen with ingestion of non-sulforaphane containing alfalfa sprouts.
Oral sulforaphane safely and effectively induces mucosal Phase II enzyme expression in the upper airway of human subjects. This study demonstrates the potential of antioxidant Phase II enzymes induction in the human airway as a strategy to reduce the inflammatory effects of oxidative stress.
This study demonstrates the potential of enhancement of Phase II enzyme expression as a novel therapeutic strategy for oxidant induced airway disease.
A placebo-controlled dose escalation trial demonstrated that naturally occurring sulforaphane from broccoli sprouts can induce a potent increase in antioxidant Phase II enzymes in airway cells.
细胞氧化应激是哮喘的一个重要因素，被认为是臭氧和颗粒物等氧化污染物介导其促炎作用的主要机制。内源性II相酶通过清除活性氧和代谢活性化学物质来消除氧化应激。
我们进行了一项安慰剂对照的剂量递增试验，以研究萝卜硫素（一种天然存在的II相酶强效诱导剂）对人类受试者上呼吸道中谷胱甘肽 - S - 转移酶M1（GSTM1）、谷胱甘肽 - S - 转移酶P1（GSTP1）、NADPH醌氧化还原酶（NQO1）和血红素加氧酶 - 1（HO - 1）表达的体内效应。
研究对象口服标准化西兰花芽匀浆（BSH）中所含的萝卜硫素剂量。在给予萝卜硫素前后，通过RT - PCR测量鼻灌洗细胞中所选II相酶的RNA表达。
所有受试者均耐受口服萝卜硫素给药，无明显不良事件。鼻灌洗细胞中II相酶表达的增加呈剂量依赖性，在以BSH制备的最高剂量200克西兰花芽时观察到最大酶诱导作用。与基线相比，所有哨兵II相酶RNA表达均有显著增加。摄入不含萝卜硫素的苜蓿芽未观察到II相酶诱导作用。
口服萝卜硫素可安全有效地诱导人类受试者上呼吸道黏膜II相酶表达。本研究证明了在人类气道中诱导抗氧化II相酶作为减少氧化应激炎症作用策略的潜力。
本研究证明了增强II相酶表达作为氧化应激诱导气道疾病新治疗策略的潜力。
一项安慰剂对照的剂量递增试验表明，西兰花芽中天然存在的萝卜硫素可使气道细胞中的抗氧化II相酶显著增加。
