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.

Vitamin C protects against in vitro cytotoxicity of cypermethrin in rat hepatocytes.

The objective of this study was to investigate the effect of ascorbic acid (AA) on the in vitro cytotoxicity of cypermethrin (CM), and on glutathione (GSH) metabolism in rat hepatocytes. In vitro cell viability, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) leakage were measured, as indicators of hepatic damage, at 1, 15 and 30 min of exposure to CM. Glutathione and the activities of glutathione-S-transferase (GST) and gamma glutamyl transpeptidase (gamma-GT) were also measured. CM hepatotoxicity increased in a time and dose-dependent manner. In the presence of 30 microM CM, ALT and AST also increased 49 and 130% (P < 0.05), respectively, indicating metabolic hepatocyte damage. AA (1 mM) was capable to preserve 100% of cell integrity and modulated ALT and AST. Furthermore, CM induced a 27% reduction in the endogenous antioxidant GSH, and increased 203% GST and 283% gamma-GT (P < 0.05), indicating an oxidative insult. The presence of AA showed chemopreventive capacity against CM, recovering 60% of GSH and a 54% decrease in gamma-GT activity. These results suggest that AA in a 1:33 (CM:AA) ratio can modulate up to 90% of the damage caused to the cells by CM. It also demonstrates that AA can act as a primary antioxidant and hepatoprotector in rat hepatocytes.