Abstract

Oxidant stress is a factor in the development of allergic sensitization and asthma by triggering an inflammatory response. Well‐characterized Diesel Exhaust Particles (DEP) have been shown in vitro and in animals to induce inflammatory and pro‐allergic effects that can be abrogated by antioxidants, but this has not been demonstrated in humans. In phase 1 of this clinical study, a suspension containing a small amount of DEP was administered intranasally in 19 atopic human subjects with known cat allergy, inducing an inflammatory response in 14 subjects characterized by increased neutrophil cell counts >10K/ml3 in the nasal washing fluid 24 hours after DEP challenge. Sulforaphane (SFN) in broccoli is a potent inducer of phase II enzymes and antioxidant response via activation of Nrf2. To test whether broccoli sprout extract (Broccosprout®; BSE) could inhibit the inflammatory response caused by DEP, 14 subjects responding to DEP challenge in phase 1 entered phase 2 of the study after a 4 week washout. BSE was administered as a single oral AM dose (>100 μmol/g SFN diluted with mango juice) daily for 4 days. DEP challenge was carried out before and after BSE consumption. After DEP exposure average cell count increased 235.9±83.7% (p=0.02) at 24 h, but no significant increases were seen in cell count after 4 days of oral BSE administration (1.7±41.5%, p=0.02). BSE effects on a panel of cytokines in the nasal washes are being evaluated. These studies provide a model in which preventive and therapeutic strategies targeting asthma and allergic diseases can be developed based on the inhibition of oxidant stress through the action of phytochemicals such as SFN.Research Supported by the UCLA Asthma Center NIH Grant No. 1 U19‐AI 070453.

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