Pacheco Gustavo S, Panatto Jordana P, Fagundes Diego A, Scaini Giselli, Bassani Cintia, Jeremias Isabela C, Rezin Gislaine T, Constantino Larissa, Dal-Pizzol Felipe, Streck Emilio L
Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil.
Metab Brain Dis. 2009 Sep;24(3):383-94. doi: 10.1007/s11011-009-9143-8. Epub 2009 Aug 18.
Encephalopathy is an important cause of morbidity and mortality in patients with severe hepatic failure and the mechanisms underlying hepatic encephalopathy are still not fully known. Considering that creatine kinase (CK) play a crucial role in brain energy homeostasis and is inhibited by free radicals, and that oxidative stress is probably involved in the pathogenesis of hepatic encephalopathy, we evaluated CK activity in hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex of rats submitted to acute administration of carbon tetrachloride or acetaminophen. The effects of the administration of antioxidants, N-acetylcysteine (NAC) plus deferoxamine (DFX) in association, and taurine, were also evaluated. Our findings demonstrated that carbon tetrachloride inhibited CK activity in cerebellum; acetaminophen inhibited the enzyme in cerebellum and hippocampus. CK activity was not affected in other brain areas. The administration of NAC plus DFX reversed the inhibition of CK activity caused by carbon tetrachloride in cerebellum and by acetaminophen in cerebellum and hippocampus. On the other hand, taurine was not able to reverse the inhibition in CK activity. Although it is difficult to extrapolate our findings to the human condition, the inhibition of brain CK activity after hepatic failure may be involved in the pathogenesis of hepatic encephalopathy.
肝性脑病是严重肝衰竭患者发病和死亡的重要原因，其潜在机制仍未完全明确。鉴于肌酸激酶（CK）在脑能量稳态中起关键作用且受自由基抑制，同时氧化应激可能参与肝性脑病的发病机制，我们评估了急性给予四氯化碳或对乙酰氨基酚的大鼠海马、纹状体、小脑、大脑皮层和前额叶皮层中的CK活性。还评估了联合给予抗氧化剂N - 乙酰半胱氨酸（NAC）加去铁胺（DFX）以及牛磺酸的效果。我们的研究结果表明，四氯化碳抑制小脑的CK活性；对乙酰氨基酚抑制小脑和海马的该酶活性。其他脑区的CK活性未受影响。给予NAC加DFX可逆转四氯化碳对小脑以及对乙酰氨基酚对小脑和海马所致的CK活性抑制。另一方面，牛磺酸无法逆转CK活性的抑制。尽管难以将我们的研究结果外推至人类情况，但肝衰竭后脑CK活性的抑制可能参与肝性脑病的发病机制。
