POSTER PRESENTATION ABSTRACTS
Please note: All posters will be displayed in Salons 10-12.

THURSDAY, 10:15-11:00 AM

---

Sakata Y, Zhuang H, Doré S*.

Potential new mechanisms to explain the French paradox by increasing cell resistance against oxidative stress.

Johns Hopkins University, SOM, ACCM Dept & Neuroscience Dept sdore@jhmi.edu *Presenting author

PURPOSE: Stilbene/Polyphenolic compounds, such as resveratrol, quercetin, and catechin are naturally present at high concentrations in grape skin, seeds, and red wine. Epidemiologic studies have shown that a reduced incidence of cardiovascular risk has been associated with consumers of red wine; this has become popularized as the "French Paradox". Resveratrol has been shown to have significant antioxidant properties in a variety of in vitro and in vivo models and to inhibit lipid peroxidation in induced models. It also has been shown to reduce ischemic damage in ischemia/reperfusion injury in isolated heart and ischemia/reperfusion in the brain. Further, it has been shown to be protective against glutamate toxicity and nitric oxide-induced toxicity. We have specifically tested whether the heme oxygenase (HO) neuroprotective enzyme could be stimulated after resveratrol treatment. We have previously shown that pharmacologic inhibition of HO activity produced an infarct size almost twice larger than in control mice, while another group revealed that HO1 overexpression within neurons can significantly reduce infarct size. We questioned whether an increase in HO1 by resveratrol is a unique pathway by which this compound can exert its neuroprotective actions.

METHODS: Cultures of cortical neuronal cells were isolated from mice and maintained in serum-free high glucose neurobasal medium. After 10Ð14 days in culture, cells were treated with resveratrol and other polyphenols. Western blots were used to determine protein expression. Glutamate was used to induce excitotoxicity. In order to address specificity, cells were incubated with the HO inhibitor SnPPIX or the vehicle control. Cell survival was evaluated by measuring mitochondria activity.

RESULTS: We found that resveratrol can induce HO1 in a dose- and time-dependent manner with a maximal induction at 25 µM and after 6-hr exposure. Resveratrol has no effect on either HO2 protein expression or cytochrome P450 reductase expression, the latter being required for maximal HO activity. Moreover, resveratrol does not appear to be toxic to mouse primary cortical neurons when they are treated for 24 hr at concentrations up to 100 µM. We found that resveratrol at 25 µM can protect mouse cortical cells from glutamate toxicity by about 60%. The use of a specific HO inhibitor (SnPPIX) completely eliminates resveratrol's protective effects observed in primary neurons.

CONCLUSIONS: The beneficial effects often associated with moderate consumption of red wines could be explained by induction of heme oxygenase 1 through resveratrol. More work is required before suggesting a possible prophylactic use of red wine against cerebrovascular disorders.

 

Back