Study of the ameliorating effects of an enteral nutrient for liver failure on hepatic encephalopathy: effects of SF-1008C on plasma and brain free amino acids, intracerebral amine concentrations and electroencephalogram in portacaval shunted rats with ammonia loading

Abstract

The ameliorating effects of an enteral nutrient for liver failure (SF-1008C), which is enriched with branched-chain amino acids (BCAA) and includes few aromatic amino acids (AAA), were investigated. The blood ammonia, plasma and brain free amino acids, intracerebral amine concentrations and electroencephalogram were measured in portacaval shunted rats with 10% ammonium acetate (3 ml/kg, i.p.) (PCS) as a model of hepatic encephalopathy. The blood ammonia and plasma free amino acid concentrations in PCS rats were significantly increased in comparison to sham-operated (Sham) rats. Thus, the plasma BCAA/AAA ratio in PCS rats was appreciably reduced. Concomitant with the abnormal plasma amino acid concentrations, the brain free amino acid concentrations in PCS rats were markedly increased in comparison to the Sham rats. Moreover, the intracerebral tryptophan (Trp) and 5-hydroxyindol acetic acid (5-HIAA) concentrations were significantly increased, and the intracerebral dopamine (DA) concentration was significantly decreased in the PCS rats. The intracerebral serotonin (5-HT) and norepinephrine (NE) concentrations were, however, hardly changed. A smaller voltage for the electroencephalogram was used in the PCS rats than in the Sham rats. Abnormal plasma and brain free amino acid concentrations in PCS rats were normalized by oral administration of SF-1008C, and the low voltage electroencephalograms in the PCS rats were suppressed. On the other hand, abnormal plasma and brain free amino acid concentrations in the PCS rats were hardly normalized by oral administration of ED-AC, an elemental diet based on an amino acid composition of egg protein. These results suggest that SF-1008C affects brain free amino acids, intracerebral amine concentrations and electroencephalogram by ameliorating abnormal plasma free amino acid concentrations. Moreover, there is a highly significant correlation between the plasma BCAA/AAA ratio and the brain BCAA/AAA ratio, and this finding suggests that the plasma free amino acid patterns reflect the brain free amino acid patterns.