Brain creatine kinase activity is inhibited after hepatic failure induced by carbon tetrachloride or acetaminophen.
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.
Pacheco
Gustavo S
GS
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.
Panatto
Jordana P
JP
Fagundes
Diego A
DA
Scaini
Giselli
G
Bassani
Cintia
C
Jeremias
Isabela C
IC
Rezin
Gislaine T
GT
Constantino
Larissa
L
Dal-Pizzol
Felipe
F
Streck
Emilio L
EL
D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology*; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology*; D003402:Creatine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D007677:Kidney Function Tests; D017093:Liver Failure / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D000082:Acetaminophen; D000410:Alanine Transaminase; D003402:Creatine Kinase
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