Institute for Scientific Interdisciplinary Studies, CH-6600 Locarno and Faculty of Sciences, University of Lausanne, Lausanne, Switzerland (G. A. Losa).
Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells
Article first published online: 18 AUG 2003
European Journal of Clinical Investigation
Volume 33, Issue 9, pages 818–823, September 2003
How to Cite
Losa, G. A. (2003), Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells. European Journal of Clinical Investigation, 33: 818–823. doi: 10.1046/j.1365-2362.2003.01219.x
- Issue published online: 18 AUG 2003
- Article first published online: 18 AUG 2003
- Received 17 January 2003; accepted 22 May 2003
- oxidative stress;
- PBMN cells;
Background We examined the effect of resveratrol (RS), a nonflavonoid polyphenolic phytoalexin found in grapes and red wine, and RS coincubated with the oxidant 2-deoxy-D-ribose (dR), on apoptosis and on the oxidative metabolic status of normal human peripheral blood mononuclear cells (PBMNCs) isolated ex vivo from healthy donors.
Material and methods Apoptosis was measured by changes of membrane permeability to propidium iodide (PI), plasma membrane exposure of phosphatidylserine (PS) and intracellular caspase activity. Oxidative status was assessed by recording the intracellular glutathione concentration (GSH), the activities of the enzymes y-glutamyltransferase (y-GT) and glutathione-S-transferase (GST), and intracellular lipid peroxidation (MDA).
Results Neither apoptotic nor oxidative parameters were affected by culturing PBMNCs in medium containing RS up to 20 µM for 5 days, while the frequency of cells with intermediate permeability to PI (17% ± 5) increased at 50 µM of RS. Thus resveratrol was slightly toxic, but there was little apoptosis in these cells. Peripheral blood mononuclear cells were also grown first in medium plus RS for 24 h and then for 96 h in medium containing RS plus 10 mM of dR, an oxidant sugar that is apoptogenic for human lymphocytes. The apoptotic changes triggered by dR were counteracted by the phytoalexin in a dose-dependent manner, but RS activity was absent at the lowest concentration (5 µM) and significantly reduced at the highest concentration used (50 µM). In PBMNCs coincubated with 20 µM of RS and 10 mM of dR the antioxidant effect of RS manifested with a significant reduction of caspases-3, -8, y-GT, GST activities and MDA content.
Conclusions Peripheral blood mononuclear cells acquire antioxidant capacity when treated with RS. Grape resveratrol may make a useful dietary supplement for minimizing oxidative injury in immune-perturbed states and human chronic degenerative diseases.