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Abstract
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.