The anti-oxidant potential of different flavonoids in human bronchial epithelial cells

Abstract

Oxidative stress is known to play a pathogenetic role in neurodegenerative, cardiovascular, lung and liver diseases. It increases as a result of an imbalance between the production of oxidants and the activity of the antioxidant defense system. The antioxidants and free radical scavengers eliminate the excessive reactive oxygen species, prevent their formation and promote the activity of endogenous anti-oxidant mechanism. Flavonoids are well-known to possess anti-oxidant properties. In the present study, the anti-oxidant potentials of different flavonoids from different sub-families were examined in airway epithelial cells. Moreover, experiments were designed to examine whether or not flavonoids reduce the oxidative stress in the airway epithelium due to bacterial infection, and if so, whether or not they produce the effects by activating the two major endogenous anti-oxidant systems, catalase and glutathione.

Human bronchial epithelial BEAS-2B cells were treated with different flavonoids in the absence and presence of the bacterial endotoxin, lipopolysaccharides (LPS). The concentration of 8-isoprostane, a biomarker for oxidative stress, in the culture medium was measured, as an indication of the antioxidant potentials of the flavonoids. The activity of catalase and the cellular level of glutathione in BEAS-2B cells after the treatments were also evaluated. Among the 17 flavonoids tested, pelargonidin was the only flavonoid that could reduce 8-isoprostane levels in conditions with and without LPS. Quercetin showed an anti-oxidant effect only in cells without LPS treatment while phloretin reduced 8-isoprostane level only in cells treated with LPS. Daidzein was found to have a pro-oxidant effect in the presence of LPS. Unexpectedly, quercetin reduced catalase activity in BEAS-2B cells not treated with LPS, and had no effect on the cellular glutathione level. Daidzein did not affect catalase activity and glutathione level, similarly to catechin[which served as the “negative control” for flavonoids in the study(as it did not affect the 8-isoprostane level in conditions with and without LPS)].

In conclusion, not all flavonoids produce anti-oxidant effects in human bronchial epithelial cells; only quercetin, pelargonidin and phloretin appear to offer anti-oxidative protection. However, quercetin inhibits catalase in BEAS-2B cells without LPS treatment, thus suggesting a possible pro-oxidant action under basal conditions. Therefore, cautions should be taken in considering the use of quercetin as a health supplement against cellular oxidative stress. Similarly, the observation that daidzein may have pro-oxidant effects in conditions with LPS also poses a warning for the use of this flavonoid as a health supplement. The proposal that flavonoids have pro-oxidant effects appears contradictive with their reported effects in some other studies; the discrepancy may be explained by the differences in the cell types, the biomarker and the concentration of flavonoid used. Therefore, the present findings prompt the need for a comprehensive assessment of the anti-oxidant potential of the flavonoids in different cell types and various conditions in order to consider their applications as anti-oxidants.