Hypotaurine is an Energy-Saving Hepatoprotective Compound against Ischemia-Reperfusion Injury of the Rat Liver
Hypotaurine is an Energy-Saving Hepatoprotective Compound against Ischemia-Reperfusion Injury of the Rat Liver
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DOI：
10.3164/jcbn.09-91
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发表时间：
2010-03-01
影响因子：
2.4
通讯作者：
Suematsu, Makoto
中科院分区：
文献类型：
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作者：
Sakuragawa, Tadayuki;Hishiki, Takako;Suematsu, Makoto
毛细管电泳质谱(CE-MS)辅助的代谢组分析使我们能够系统地掌握小分子代谢物在疾病条件下的变化。我们应用CE-MS来挖掘肝脏缺血再灌注的生物标志物。通过阻断门静脉入口，然后再灌流的方法，使大鼠肝脏处于缺血状态。代谢组学分析显示，1牛磺酸在肝脏和血浆中的含量显著增加。有趣的是亚牛磺酸的升高，共同表明亚牛磺酸/牛磺酸在缺血后反应中的重要性。考虑到次牛磺酸的抗氧化能力，我们考察了补充该化合物或其前体氨基酸是否会影响肝细胞活力以及肝脏和血浆中牛磺酸的含量。再灌流时给予次牛磺酸、N-乙酰半胱氨酸或蛋氨酸可明显减轻缺血后肝细胞损伤，但组间代谢组学特征不同：蛋氨酸或N-乙酰半胱氨酸治疗组大鼠肝脏乳酸生成量显著增加，而能量电荷未见明显恢复。此外，接受次牛磺酸治疗的那一组的血浆牛磺酸水平升高，这表明外源性给予的化合物被用作抗氧化剂。这些结果表明，牛磺酸可作为缺血再灌注的替代标志物，提示次牛磺酸作为一种节能的保护肝脏的氨基酸是有效的。
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 1 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 hepato-protective amino acid.