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Keywords:

  • apoptosis;
  • cyclooxygenase;
  • lipoxygenase;
  • oxidative stress;
  • resveratrol

The natural polyphenolic compound resveratrol (trans-3,4′,5-trihydroxystilbene) is shown to prevent apoptosis (programmed cell death) induced in human erythroleukemia K562 cells by hydrogen peroxide and other unrelated stimuli. Resveratrol reversed the elevation of leukotriene B4 (from 6.40 ± 0.65 to 2.92 ± 0.30 pmol·mg protein−1) and prostaglandin E2 (from 11.46 ± 1.15 to 8.02 ± 0.80 nmol·mg protein−1), induced by H2O2 challenge in K562 cells. The reduction of leukotriene B4 and prostaglandin E2 correlated with the inhibition of the 5-lipoxygenase activity, and the cyclooxygenase and peroxidase activity of prostaglandin H synthase, respectively. Resveratrol also blocked lipoperoxidation induced by hydrogen peroxide in K562 cell membranes. Resveratrol was found to act as a competitive inhibitor of purified 5-lipoxygenase and 15-lipoxygenase and prostaglandin H synthase, with inhibition constants of 4.5 ± 0.5 µm (5-lipoxygenase), 40 ± 5.0 µm (15-lipoxygenase), 35 ± 4.0 µm (cyclooxygenase activity of prostaglandin H synthase) and 30 ± 3.0 µm (peroxidase activity of prostaglandin H synthase). Altogether, the results reported here suggest that the anti-apoptotic activity of resveratrol depends on the direct inhibition of the main arachidonate-metabolizing enzymes.