Inhibition of Hydrogen Peroxide-Induced Endothelial Apoptosis by 2′,4′,7-Trihydroxyflavanone, a Flavonoid Form
- 1 December 2004
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Medicinal Food
- Vol. 7 (4), 408-416
- https://doi.org/10.1089/jmf.2004.7.408
Abstract
Oxidative stress contributes to cellular injury following clinical and experimental ischemia/reperfusion episodes. Oxidative injury can induce cellular and subcellular damage that results in apoptotic cell death. We tested whether 2′,4′,7-trihydroxyflavanone, a synthetic flavonoid derivative, inhibits hydrogen peroxide (H2O2)-induced toxicity in human umbilical endothelial cells (HUVECs). Cultured HUVECs were incubated for 30 minutes with 0.2 mM H2O2 in the absence and presence of 2′,4′,7-trihydroxyflavanone at a non-toxic concentration of 50 µM. The effect of 2′,4′,7-trihydroxyflavanone on apoptosis parameters was compared with that of naringenin and two flavonol derivatives, 2′,4′,7-trihydroxyflavonol and 2′,4′,6-trihydroxyflavonol. H2O2 induced cell death within 24 hours over the range of 0.05–1.0 mM, and decreased cell viability by ∼30% at 0.2 mM. This cytotoxicity was associated with nuclear condensation and DNA fragmentation, indicating induction of apoptosis. 2′,4′,7-Trihydroxyflavanone, as well as naringenin, was effective as an inhibitor of oxidative stress, protecting cell viability with ≥85% viable cells compared with the control, and no apparent nuclear condensation or DNA fragmentation. In contrast, the flavonol derivatives had no such effect. In addition, immunocytochemical data and Western blot analysis revealed that, unlike flavonol derivatives, the expression of Bcl-2 was markedly up-regulated, and that the expression of Bax and activation of caspase-3 were strongly inhibited by this flavanone derivative, thereby implicating antioxidant activity-related anti-apoptotic mechanisms of 2′,4′,7-trihydroxyflavanone. These results indicate that the synthetic flavonoid derivative 2′,4′,7-trihydroxyflavanone is an effective antioxidant, preventing endothelial apoptosis induced by H2O2.Keywords
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