Metabolomic analysis of sulfur-containing substances and polyamines in regenerating rat liver

Abstract

We studied the significance of alterations in the metabolomics of sulfur-containing substances in rapidly regenerating rat livers. Male rats were subjected to two-thirds partial hepatectomy (PHx), and the changes in hepatic levels of major sulfur-containing amino acids and related substances were monitored for 2weeks. Liver weight began to increase from 24h after the surgery, and appeared to recover fully in 2weeks. Serum alanine aminotransferase and aspartate aminotransferase activities were elevated immediately after the surgery and returned slowly to normal levels in 2weeks. Methionine, S-adenosylmethionine (SAM), cystathionine and cysteine were increased rapidly and remained elevated for longer than 1week. Hepatic glutathione concentration was increased gradually for 24h, and then decreased thereafter, whereas hypotaurine was elevated drastically right after the surgery. Hepatic concentrations of polyamines were altered significantly by PHx. In the hepatectomized livers putrescine concentration was elevated rapidly, reaching a level 40- to 50-fold greater than normal in 6-12h. Ornithine, the metabolic substrate for putrescine synthesis, was also elevated markedly. Spermidine was increased significantly, whereas spermine was depressed below normal, which appeared to be due to the increased consumption of decarboxylated SAM for spermidine biosynthesis. The results show that the metabolomics of sulfur-containing amino acids and related substances is altered profoundly in regenerating rat livers until the original weight is recovered. Hepatic concentrations of polyamines after PHx are closely associated with the alteration in the metabolomics of sulfur-containing substances. The implication of these changes in the progression of liver regeneration is discussed.