Functional changes of brain mitochondria during experimental hepatic encephalopathy

Several functional parameters were studied in a non-synaptic population of brain mitochondria from rats made cirrhotic by chronic treatment with carbon tetrachloride, with and without coma produced by a single injection of ammonium acetate. The following changes were observed in mitochondria from cirrhotic rats, independently of the presence of coma: (a) a large decrease in oxygen consumption with pyruvate-malate as substrate, but not with succinate, in both states 3 and 4; (b) a modified volume oscillation pattern, characterized by a notable diminution in the amplitude of the oscillation; (c) an altered pattern of acyl groups, with a decrease in the proportion of unsaturated with respect to saturated fatty acids. The following parameters were also measured in brain mitochondria from the cirrhotic rats and were found unchanged: (a) malate dehydrogenase and ATPase activities; (b) content of cytochromes; (c) phospholipid composition; (d) total fatty acid content. The possible significance of the changes observed is discussed in terms of the membranal and biochemical alterations that may be involved in the mechanism of hepatic encephalopathy.