Antioxidant defense in the rat brain cortex, cerebellum, hippocampus, and striatum and its alterations during portacaval shunting

Abstract

Portacaval anastomoses spontaneously appear during liver insufficiency and lead to chronic hyperammonemia and hepatic encephalopathy. Ammonium induces oxidative stress in the brain. Here, we compared the state of the antioxidant system in different rat brain areas and studied the manner in which it is affected by portacaval shunting. At 4 weeks after the surgical operation, we measured the activities of catalase, Cu,Zn-superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione transferase in cytoplasm and content of oxidized proteins in mitochondria of the neocortex, cerebellum, hippocampus, and striatum. All four brain regions differed according to the ammonium content and activity of each antioxidant enzyme. The activity of glutathione peroxidase decreased as compared to the control only in the cerebellum and striatum of animals with portacaval shunt. After portacaval shunting, the activities of catalase, Cu,Zn-superoxide dismutase, glutathione peroxidase, and glutathione reductase did not differ from the control in all the brain regions we studied. An inverse correlation between the content of oxidized proteins and activity of glutathione transferase suggests that the diminished activity of glutathione peroxidase in the cerebellum and striatum, but not other antioxidant enzymes and other brain regions, may play a role in the pathogenesis of hepatic encephalopathy.