INCREASED BRAIN CONCENTRATIONS OF POLYAMINES IN RATS WITH ENCEPHALOPATHY DUE TO A GALACTOSAMINE-INDUCED FULMINANT HEPATIC-FAILURE

Polyamine concentrations including putrescine, spermidine and spermine were documented in two brain areas of rats with mild and severe stage s of hepatic encephalopathy (HE) due to fulminant hepatic failure indu ced by galactosamine HCl injection (3 g kg(-1) i.p.). In the mild stag e of HE putrescine increased by 3-4 times whereas spermidine and sperm ine showed a slight increase. The scenario, however, was found to be c hanged going from the mild to the severe stage of HE, since in this la st stage spermidine and spermine showed a further rise while putrescin e was found to be significantly lower than in the mild stage of HE in both the brain areas studied. The changes in the ratio among the three polyamines with an enhanced prevalence in the severe stage of HE of s permidine and spermine are likely to be related to the exhaustion of t he synthetic pathway of putrescine or to a reduction of the interconve rsion to this polyamine from spermidine and spermine. Considering that these last two polyamines potentiate the N-methyl-D-aspartate glutama te receptor mediated toxicity and that they might exert neurotoxic eff ects per se, there are clear reasons for suspecting an implication of the described changes of polyamines in the neurochemical mechanism whi ch sustain HE and to surmise a potential therapeutic effect in this pa thology of non-competitive antagonists of polyamine-site on N-methyl-D -aspartate glutamate receptors. (C) 1995 The Italian Pharmacological S ociety