M Wettstein1, D Häussinger. 1. Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Düsseldorf, Germany.
Abstract
BACKGROUND: Taurine, betaine, and inositol were recently identified as osmolytes in liver cells interfering with cell volume regulation and cell function. In this study, the effect of osmolytes on cold ischemia-reoxygenation injury was investigated in rat liver. METHODS AND RESULTS: Isolated rat livers were flushed for 15 min with Krebs-Henseleit buffer (KHB), then stored for 16 hr in KHB at 4 degrees C, and thereafter reperfused with oxygenated KHB for 180 min. When taurine, betaine, and inositol (2 mmol/L, each) were added to the preperfusion and storage buffer, lactate dehydrogenase, aspartate amino transferase, and glutathione S-transferase leakage into the effluent perfusate during the reoxygenation period were less than half compared to controls without osmolytes and bile flow was higher. The effect of taurine (2 mmol/L) was similar to a mixture of all three osmolytes, indicating that taurine is the most important constituent. When livers were stored for 24 hr in University of Wisconsin solution, osmolyte addition to the storage solution also decreased lactate dehydrogenase and aspartate aminotransferase leakage during reoxygenation. Increasing liver taurine content by a 7-day taurine supplementation of drinking water attenuated reoxygenation injury in cold and warm ischemia in rat livers, whereas taurine depletion by beta-alanine feeding had the opposite effect. CONCLUSIONS: The data show that taurine protects livers from ischemia-reoxygenation. Taurine addition to perfusion and storage solutions in low millimolar concentrations or taurine supplementation of the donor may be useful to protect transplanted organs.
BACKGROUND:Taurine, betaine, and inositol were recently identified as osmolytes in liver cells interfering with cell volume regulation and cell function. In this study, the effect of osmolytes on cold ischemia-reoxygenation injury was investigated in rat liver. METHODS AND RESULTS: Isolated rat livers were flushed for 15 min with Krebs-Henseleit buffer (KHB), then stored for 16 hr in KHB at 4 degrees C, and thereafter reperfused with oxygenated KHB for 180 min. When taurine, betaine, and inositol (2 mmol/L, each) were added to the preperfusion and storage buffer, lactate dehydrogenase, aspartate amino transferase, and glutathione S-transferase leakage into the effluent perfusate during the reoxygenation period were less than half compared to controls without osmolytes and bile flow was higher. The effect of taurine (2 mmol/L) was similar to a mixture of all three osmolytes, indicating that taurine is the most important constituent. When livers were stored for 24 hr in University of Wisconsin solution, osmolyte addition to the storage solution also decreased lactate dehydrogenase and aspartate aminotransferase leakage during reoxygenation. Increasing liver taurine content by a 7-day taurine supplementation of drinking water attenuated reoxygenation injury in cold and warm ischemia in rat livers, whereas taurine depletion by beta-alanine feeding had the opposite effect. CONCLUSIONS: The data show that taurine protects livers from ischemia-reoxygenation. Taurine addition to perfusion and storage solutions in low millimolar concentrations or taurine supplementation of the donor may be useful to protect transplanted organs.