Baraldi M, Zeneroli M L, Zanoli P, Truzzi C, Venturini I, Davalli P, Corti A
School of Pharmacy, Modena University, Italy.
Pharmacol Res. 1995 Jul-Aug;32(1-2):57-61. doi: 10.1016/s1043-6618(95)80009-3.
Polyamine concentrations including putrescine, spermidine and spermine were documented in two brain areas of rats with mild and severe stages of hepatic encephalopathy (HE) due to fulminant hepatic failure induced by galactosamine HC1 injection (3 g kg-1 i.p.). In the mild stage of HE putrescine increased by 3-4 times whereas spermidine and spermine showed a slight increase. The scenario, however, was found to be changed going from the mild to the severe stage of HE, since in this last stage spermidine and spermine showed a further rise while putrescine 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 spermidine and spermine are likely to be related to the exhaustion of the synthetic pathway of putrescine or to a reduction of the interconversion to this polyamine from spermidine and spermine. Considering that these last two polyamines potentiate the N-methyl-D-aspartate glutamate receptor mediated toxicity and that they might exert neurotoxic effects per se, there are clear reasons for suspecting an implication of the described changes of polyamines in the neurochemical mechanism which sustain HE and to surmise a potential therapeutic effect in this pathology of non-competitive antagonists of polyamine-site on N-methyl-D-aspartate glutamate receptors.
通过腹腔注射盐酸半乳糖胺（3 g/kg）诱导暴发性肝衰竭，从而在患有轻度和重度肝性脑病（HE）的大鼠的两个脑区记录了包括腐胺、亚精胺和精胺在内的多胺浓度。在HE的轻度阶段，腐胺增加了3至4倍，而亚精胺和精胺略有增加。然而，从HE的轻度阶段到重度阶段，情况发生了变化，因为在重度阶段，亚精胺和精胺进一步升高，而在所研究的两个脑区中，腐胺均显著低于HE的轻度阶段。在HE的重度阶段，亚精胺和精胺的患病率增加，三种多胺之间的比例变化可能与腐胺合成途径的耗尽或从亚精胺和精胺向该多胺的相互转化减少有关。考虑到后两种多胺会增强N-甲基-D-天冬氨酸谷氨酸受体介导的毒性，并且它们本身可能会产生神经毒性作用，因此有充分的理由怀疑所描述的多胺变化与维持HE的神经化学机制有关，并推测多胺位点非竞争性拮抗剂对N-甲基-D-天冬氨酸谷氨酸受体在这种病理状态下具有潜在的治疗作用。
