Phenylbutyrate exerts adverse effects on liver regeneration and amino acid concentrations in partially hepatectomized rats
Abstract
Phenylbutyrate is recommended in urea cycle disorders and liver injury to enhance nitrogen disposal by the urine. We report the effects of phenylbutyrate on liver regeneration and amino acid levels in plasma of partially hepatectomized (PH) rats.
Phenylbutyrate or saline was administered at 12-h intervals to PH or laparotomized rats. Phenylbutyrate delayed the onset of liver regeneration compared to saline-treated controls, as indicated by lower hepatic DNA specific activities 18 and 24 hours post-PH, decreased hepatic fractional protein synthesis rates 24 hours post-PH, and lowered the increases in liver weights and hepatic protein and DNA contents 48 hours after PH.
Hepatic DNA fragmentation (a hallmark of apoptosis) was higher in phenylbutyrate-treated animals than in controls. Phenylbutyrate decreased the glutamine and BCAA concentrations and the ratio of the BCAA to aromatic amino acids (phenylalanine and tyrosine) in the blood plasma in both hepatectomized and laparotomized animals.
In conclusion, the delayed onset of liver regeneration and the decrease in BCAA to aromatic amino acid ratio in blood suggest that phenylbutyrate administration may be disastrous in subjects with acute hepatic injury and BCAA supplementation is needed when phenylbutyrate is used therapeutically.