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 in the treatment of experimental stroke in rats, mainly by inhibition of the glutamate-activated NO pathway, but also by counteracting osmotic stress by a mechanism associated with the release of the osmotically active amino acid taurine (Tau). Here we show that lubeluzole administered i.p. decreases by 25% the high (50 mM) K+-evoked accumulation of Tau in striatal microdialysates of healthy rats and by 34% in rats with thioacetamide-induced hepatic failure, where the increased extracellular accumulation of Tau signifies ongoing hepatic encephalopathy. Lubeluzole does not affect the nonstimulated accumulation of Tau in either group of rats. The results indicate that lubeluzole may be effective in ameliorating ionic or osmotic stress in a range of pathological conditions involving the rise of extracellular K+, and also in decreasing the vulnerability to stress in rats with hepatic failure.
Zielińska
M
M
Department of Neurotoxicology, Medical Research Centre, Polish Academy of Sciences, Pawiñskiego St. 5, 02-106, Warsaw, Poland.
Hilgier
W
W
Borkowska
H D
HD
Oja
S S
SS
Saransaari
P
P
Albrecht
J
J
D000818:Animals; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009997:Osmotic Pressure / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D013853:Thioacetamide / Q000494:pharmacology
D018696:Neuroprotective Agents; D010880:Piperidines; D013844:Thiazoles; D013853:Thioacetamide; D013654:Taurine; D018698:Glutamic Acid; D011189:Potassium Chloride; C097722:lubeluzole