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Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway.

Abstract

BACKGROUND

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.

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

CLINICAL IMPLICATIONS

This study demonstrates the potential of enhancement of Phase II enzyme expression as a novel therapeutic strategy for oxidant induced airway disease.

CAPSULE SUMMARY

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.

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  • Authors+Show Affiliations

    ,

    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. mriedl@mednet.ucla.edu

    ,

    Source

    Clinical immunology (Orlando, Fla.) 130:3 2009 Mar pg 244-51

    MeSH

    Administration, Oral
    Adult
    Antioxidants
    Brassica
    Enzymes
    Female
    Gene Expression Regulation, Enzymologic
    Glucosinolates
    Glutathione Transferase
    Heme Oxygenase-1
    Humans
    Isothiocyanates
    Male
    Middle Aged
    NAD(P)H Dehydrogenase (Quinone)
    Nasopharynx
    Thiocyanates
    Up-Regulation
    Young Adult

    Pub Type(s)

    Clinical Trial
    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    19028145

    Citation

    Riedl, Marc A., et al. "Oral Sulforaphane Increases Phase II Antioxidant Enzymes in the Human Upper Airway." Clinical Immunology (Orlando, Fla.), vol. 130, no. 3, 2009, pp. 244-51.
    Riedl MA, Saxon A, Diaz-Sanchez D. Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Clin Immunol. 2009;130(3):244-51.
    Riedl, M. A., Saxon, A., & Diaz-Sanchez, D. (2009). Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Clinical Immunology (Orlando, Fla.), 130(3), pp. 244-51. doi:10.1016/j.clim.2008.10.007.
    Riedl MA, Saxon A, Diaz-Sanchez D. Oral Sulforaphane Increases Phase II Antioxidant Enzymes in the Human Upper Airway. Clin Immunol. 2009;130(3):244-51. PubMed PMID: 19028145.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. AU - Riedl,Marc A, AU - Saxon,Andrew, AU - Diaz-Sanchez,David, Y1 - 2008/11/22/ PY - 2008/10/07/received PY - 2008/10/09/accepted PY - 2008/11/26/pubmed PY - 2009/3/4/medline PY - 2008/11/26/entrez SP - 244 EP - 51 JF - Clinical immunology (Orlando, Fla.) JO - Clin. Immunol. VL - 130 IS - 3 N2 - BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL IMPLICATIONS: This study demonstrates the potential of enhancement of Phase II enzyme expression as a novel therapeutic strategy for oxidant induced airway disease. CAPSULE SUMMARY: 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. SN - 1521-7035 UR - https://www.unboundmedicine.com/medline/citation/19028145/Oral_sulforaphane_increases_Phase_II_antioxidant_enzymes_in_the_human_upper_airway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1521-6616(08)00862-0 DB - PRIME DP - Unbound Medicine ER -