ASPALATONE, A NEW ANTIPLATELET AGENT, ATTENUATES THE NEUROTOXICITY INDUCED BY KAINIC ACID IN THE RAT

The antioxidant efficacy of aspalatone (APT; acetyl salicylic acid mal tol ester), a new antiplatelet agent, has been characterized in vivo a s well as in vitro, and several observations indicated that the antiox idant could prevent the neuroexcitation caused by oxidative stress. In this report, the effect of APT was evaluated on kainic acid (KA)-indu ced neurotoxicity, since the neurotoxicity induced by KA is, at least in part, mediated via the formation of free radicals. The results show ed that pretreatments with APT or maltol (MAL) significantly attenuate d seizure activity, oxidative stress (lipid peroxidation and protein o xidation) and the loss of hippocampal neurons induced by KA. On the ot her hand, the pretreatments with aspirin (ASP), ASP together with MAL or vitamin E failed to protect, against the toxicity produced by KA su ggesting that the mechanism of action for APT on the KA-induced neurot oxicity is different from that of ASP. These finding raise the possibi lity that salicylmaltol, a metabolite of APT, plays a role in preventi ng the neurotoxicity evoked by KA. Therefore, our results suggest that an APT-related antioxidant mechanism, which is linked to the MAL moie ty, is involved in the neuroprotective effect against KA. (C) 1997 Els evier Science Inc.