Lubeluzole attenuates K+-evoked extracellular accumulation of taurine in the striatum of healthy rats and rats with hepatic failure

Lubeluzole is a newly designed neuroprotectant which has proved effective i n the treatment of experimental stroke in rats, mainly by inhibition of the glutamate-activated NO pathway, but also by counteracting osmotic stress b y a mechanism associated with the release of the osmotically active amino a cid taurine (Tau). Here we show that lubeluzole administered i.p. decreases by 25% the high (50 mM) K+-evoked accumulation of Tau in striatal microdia lysates of healthy rats and by 34% in rats with thioacetamide-induced hepat ic failure, where the increased extracellular accumulation of Tau signifies ongoing hepatic encephalopathy. Lubeluzole does not affect the nonstimulat ed accumulation of Tau in either group of rats. The results indicate that l ubeluzole may be effective in ameliorating ionic or osmotic stress in a ran ge of pathological conditions involving the rise of extracellular Kt, and a lso in decreasing the vulnerability to stress in rats with hepatic failure. (C) 2001 Elsevier Science B.V. All rights reserved.