Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA
Address for correspondence: Sylvain Doré, Ph.D., Johns Hopkins University, School of Medicine, Dept. of Anesthesiology and Critical Care Medicine, 600 N. Wolfe Street, (Blalock 1404A), Baltimore, MD 21287, USA. Voice: 410-614-4859; fax: 410-955-7165.
sdore{at}jhmi.edu
Ann. N.Y. Acad. Sci. 993: 276-286 (2003).
Polyphenolic compounds, such as resveratrol, are naturally present
at high concentration in grape skin, seeds, and red wine. Resveratrol
is present in
cis and
trans isoforms and the major
trans isomer
is the biologically active one. Epidemiologic studies have revealed
a reduced incidence of cardiovascular risk associated with consumers
of red wine; this has been popularized as the
French paradox.
Resveratrol has been shown to have significant antioxidant properties
in a variety of
in vitro and
in vivo models. It can reduce ischemic
damage in heart ischemia reperfusion injury and also in brain
ischemia/reperfusion in rodent models. Due to the high rate
of oxygen consumption in the brain, and especially low levels
of antioxidant defense enzymes, this organ is particularly susceptible
of free radical damage. Most of the protective biological actions
associated with resveratrol have been associated with its intrinsic
radical scavenger properties. We have investigated the possibility
of other indirect pathways by which resveratrol can exert its
neuroprotective abilities. We have specifically tested whether
heme oxygenase neuroprotective enzyme could be stimulated after
resveratrol treatment. Using primary neuronal cultures, resveratrol
was able to significantly induce heme oxygenase 1, whereas vehicle
control showed no effect. No detectable toxicity was quantified.
It is well established that after stroke significant levels
of intracellular heme levels increase. The source of free heme
comes mainly from several heme-containing enzymes. Heme (iron-protoporphyrin
IX) is a pro-oxidant and its rapid degradation by heme oxygenase
is believed to be protective. Moreover, the generation of heme
metabolites can also have their own intrinsic cellular properties.
All together, increased heme oxygenase activity by resveratrol
is a unique pathway by which this compound can exert its neuroprotective
actions.
