Changes in Plasma Amino Acid Concentration and Histopathological Findings in the Process of Carbon Tetrachloride-Induced Liver Injury in Rats.

Abstract

The relationship between changes in plasma amino acid and histological findings in the process of carbon tetrachloride (CCl4)-induced liver injury was studied in rats intraperitoneally injected with CCl4 at 0.2 ml/kg twice a week for 5 weeks. The degree of CCl4-induced liver injury was evaluated by measuring serum GPT activity, and the correlation between serum GPT activity and histological changes was investigated. In the histopathological study, diffuse centrilobular necrosis, coagulation necrosis, acidophilic, ballooning and fatty degeneration, fibrosis, and the formation of pseudolobule of hepatocytes were observed in the liver after CCl4 administration. Serum GPT activity was elevated after CCl4 administration and well-correlated with the histologic score of liver injury (r=0.887, p< 0.01). The coagulation necrosis changes and the pseudolobule formation caused by fibrosis proliferation were marked in the rats showing serum GPT activity of more than 500 unit.The plasma amino acid concentrations increased in the development process of CCl4-induced liver injury except for that of branched chain amino acids, which decreased with an increase severity of liver damage. The molar ratio of Val+Ile+Leu/Tyr+Phe (Fischer ratio) decreased in parallel to the increase in severity of liver parenchymal damage. The decrease in the Fischer ratio was correlated with serum GPT (r=-0.800), serum GOT (r=-0.711) and histologic scores (r=-0.851). These results suggest that plasma amino acid imbalance occurs prior to liver cirrhosis induced by severe liver damage, and that serum GPT and GOT activities and the Fischer ratio are closely correlated to the histological findings in the development process of CCl4-induced liver injury.