Inhibition of brain creatine kinase activity after renal ischemia is attenuated by N-acetylcysteine and deferoxamine administration.
Encephalopathy may accompany acute or chronic renal failure, and the mechanisms responsible for neurological complications in patients with renal failure are poorly known. Considering that creatine kinase (CK) is important for brain energy homeostasis and is inhibited by free radicals, and that oxidative stress is probably involved in the pathogenesis of uremic encephalopathy, we measured CK activity (hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex) in brain if rats submitted to renal ischemia and the effect of administration of antioxidants (N-acetylcysteine, NAC and deferoxamine, DFX) on this enzyme. We verified that CK activity was not altered in cerebellum and striatum of rats. CK activity was inhibited in prefrontal cortex and hippocampus of rats 12h after renal ischemia. The treatment with antioxidants prevented such effect. Cerebral cortex was also affected, but in this area CK activity was inhibited 6 and 12h after renal ischemia. Moreover, only NAC or NAC plus DFX were able to prevent the inhibition on the enzyme. Although it is difficult to extrapolate our findings to the human condition, the inhibition of brain CK activity after renal failure may be associated to neuronal loss and may be involved in the pathogenesis of uremic encephalopathy.
Di-Pietro
Priscila B
PB
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.
Dias
Márcia L
ML
Scaini
Giselli
G
Burigo
Márcio
M
Constantino
Larissa
L
Machado
Roberta A
RA
Dal-Pizzol
Felipe
F
Streck
Emilio L
EL
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D001928:Brain Diseases, Metabolic / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D003402:Creatine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D007511:Ischemia / Q000150:complications; D007674:Kidney Diseases / Q000150:complications; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions; D013997:Time Factors; D016896:Treatment Outcome; D014511:Uremia / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology
D000975:Antioxidants; D003402:Creatine Kinase; D003676:Deferoxamine; D000111:Acetylcysteine