September 15, 2008
You know it's good for you in other ways, but could eating your
broccoli also help patients with chronic lung disease? It just might.
According to recent research from Johns Hopkins Medical School, a decrease in lung concentrations of NRF2-dependent antioxidants, key components of the lung's defense system against inflammatory injury, is linked to the severity of chronic obstructive pulmonary disease or COPD - in smokers. Broccoli is known to contain a compound that prevents the degradation of NFR2.
In this study, published in the second issue for September of the American Journal of Respiratory and Critical Care Medicine, researchers examined tissue samples from the lungs of smokers with and without COPD.
Their objective was to determine if there were differences in measured levels of NRF2 expression and the level of its biochemical regulators, including KEAP1, which inhibits NRF2, and DJ-1, which stabilizes it.
Previous research had shown that disruption in NRF2 expression in mice exposed to cigarette smoke caused early onset of severe emphysema.
When compared with non-COPD lungs, the lungs of patients with COPD showed markedly decreased levels of NRF2-dependent antioxidants, increased oxidative stress markers.
There was also a significant decrease in NRF2 protein with no change in NRF2 mRNA levels (indicating that it was expressed, but subsequently degraded), and similar KEAP1 levels, but a marked decrease in the level of DJ-1.
"NRF2-dependent antioxidants and DJ-1 expression was negatively associated with severity of COPD," wrote principle investigator, Shyam Biswal, Ph.D., an associate professor in the Bloomberg School's Department of Environmental Health Sciences and Division of Pulmonary and Critical Care at Hopkins. "Therapy directed toward enhancing NRF2-regulated antioxidants may be a novel strategy for attenuating the effects of oxidative stress in the pathogenesis of COPD."
While clinical trials of antioxidants have been disappointing in improving the clinical course of patients with COPD, the fourth-leading cause of death in the U.S., this study points to a possibility of benefit from restoring NRF2 levels in damaged lungs by reducing the action of KEAP1, which is an inhibitor of NRF2.
"Increasing NRF2 may also restore important detoxifying enzymes to counteract other effects of tobacco smoke," wrote Peter Barnes, D.M., of the National Heart and Lung Institute in London, in the accompanying editorial. "This has been achieved in vitro and in vivo by isothiocynate compounds, such as sulforaphane, which occurs naturally in broccoli and [wasabi]."
Sulforapane has been shown to be able to restore antioxidant gene expression in human epithelial tissue in which DJ-1 has been reduced. Isothicyanate compounds such as that found in broccoli inhibit KEAP1, and thus prevent it from degrading NRF2, according to Barnes.
"Future studies should target NRF2 as a novel strategy to increase antioxidant protection in the lungs and test its ability to decrease exacerbations and improve lung function in patients with COPD," Biswal said.
