Neuroprotective effects of gabaergic phenols correlated with their pharmacological and antioxidant properties

Abstract

Aims. Various investigations have demonstrated the protective capacity of general anesthetics as neuroprotective agents. The effects of propofol against ischemia are known to reside in its antioxidant properties and its GABAergic activity. Other aromatic alcohols have also been reported as able to protect neurons against oxidative damage. The aim of this work is to evaluate the potential neuroprotective effect of some phenols, structurally analogues of propofol, with proven GABAergic activity. These phenols include the naturally occurring compounds thymol, carvacrol and eugenol, the synthetic product chlorothymol, and the most widely used intravenous anesthetic, propofol, as a reference compound. Materials and methods. Taking primary cultures of cortical neurons as a suitable model to evaluate cellular protection against oxidative damage, we developed an injury model to test potential neuroprotective activity. The intracellular hydroperoxides were also determined. Key findings. The results showed that no compound decreased cell viability at concentrations where they were active on the GABAA receptor. In neuroprotection tests, some phenols and Vit E showed a partial protective effect against the oxidative injury. These compounds induced a clear tendency to reduce H2O2 damage, comparing production of hydroperoxides, although these last changes were statistically non-significant. Significance. Testing the intracellular oxidation levels suggests that this partial protection exerted by propofol, thymol and chlorothymol may be mediated in some way by their antioxidant activities. However, this neuroprotection is not completely correlated with the antioxidant capacity, but it approaches their relative pharmacological potency, which could be interpreted as a final effect that would involve both activities.