Hypotaurine is an Energy-Saving Hepatoprotective Compound against Ischemia-Reperfusion Injury of the Rat Liver

Abstract

Metabolome analyses assisted by capillary electrophoresis-mass spectrometry (CE-MS) have allowed us to systematically grasp changes in small molecular metabolites under disease conditions. We applied CE-MS to mine out biomarkers in hepatic ischemia-reperfusion. Rat livers were exposed to ischemia by clamping of the portal inlet followed by reperfusion. Metabolomic profiling revealed that l contents of taurine in liver and plasma were significantly increased. Of interest is an elevation of hypotaurine, collectively suggesting significance of hypotaurine/taurine in post-ischemic responses. Considering the anti-oxidative capacity of hypotaurine, we examined if supplementation of the compound or its precursor amino acids could affect hepatocellular viability and contents of taurine in liver and plasma. Administration of hypotaurine, N-acetylcysteine or methionine upon reperfusion comparablly attenuated the post-ischemic hepatocellular injury but with different metabolomic profiling among groups: rats treated with methionine or N-acetylcysteine but not those treated with hypotaurine, exhibited significant elevation of hepatic lactate generation without notable recovery of the energy charge. Furthermore, the group treated with hypotaurine exhibited elevation of the plasma taurine, suggesting that the exogenously administered compound was utilized as an antioxidant. These results suggest that taurine serves as a surrogate marker for ischemia-reperfusion indicating effectiveness of hypotaurine as an energy-saving hepatoprotective amino acid.

Semi-quantitative analyses of metabolic systems of human colon cancer metastatic xenografts in livers of superimmunodeficient NOG mice

“…Of importance were semiquantitative values of [ATP] app in the tumor-bearing liver (Fig. 3f), in the range of approximately 1–2 μmol g −1 liver, levels reasonably comparable with previous observations that determined absolute ATP contents under the snap-frozen procedures [20, 21]. Because intracellular levels of ATP are in the mmol L −1 range, current procedures for data calibration seemed to reproduce reliable intracellular concentrations of metabolites with a rapid turnover.…”

“…As reported previously [20–22], CE–MS enabled us to quantitatively determine more than 2,000 different metabolites at once in small amounts of a single liver sample. Small amounts of the frozen tissue were collected from thick section that was adjacent to the section for IMS.…”

Microscopic imaging mass spectrometry assisted by on‐tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts

“…2). Because these levels were comparable to previous observations that determined the absolute ATP contents after snap‐freezing , the samples obtained in this study were considered to be of sufficient quality.…”

Metabolomic investigation of cholestasis in a rat model using ultra‐performance liquid chromatography/tandem mass spectrometry

“…In this study, increased urinary levels of taurine and hypotaurine were observed in EHBR. Also, recent metabolomic studies have demonstrated that these metabolites are increased under several conditions such as hepatic ischemia/reperfusion injury and after partial hepatectomy in rats, suggesting the important role played by these metabolites in the repair process after cellular damage. In EHBR, reduced biliary excretion may increase their systemic exposure to harmful compounds including some bile acids and other endogenous materials.…”