Abstract
Liver ischemia-reperfusion (I/R) injury is a major complication of liver resection and transplantation. Cytokine release by activated Kupffer cells (KCs) play a central role in the inflammatory cascade of I/R injury. There is evidence that glycine may protect against liver I/R injury by inhibition of KC activity. However, its effect on bile flow, an established marker of hepatic function, and bile composition is not known. A rabbit model of hepatic lobar warm I/R was used. Under general anesthesia, the sham group (n = 6) underwent laparotomy alone for 7 h. The I/R group (n = 6) underwent 60 min of left and median lobe inflow occlusion and 6 h of reperfusion. The glycine + I/R group (n = 6) underwent a same procedure to controls after receiving glycine 5 mg/kg intravenous infusion for over 15 min. Bile flow was collected, measured, and analyzed by proton magnetic resonance spectroscopy. Glycine prevented the significant reduction in bile flow seen in I/R at 6 h reperfusion (145.0 ± 11.4 vs. 108.3 ± 28.2 μL/min/g, p = 0.011). It reduced phosphatidylcholine shedding (1.2 ± 0.8 vs. 3.0 ± 0.5 μmol/L, p = 0.001) and lactate surge (8.1 ± 4.3 vs. 26.3 ± 7.8 μmol/L, p < 0.001) compared to I/R. Glycine significantly stimulated bile acid (17.9 ± 2.8 vs. 8.9 ± 2.1 μmol/L, p = 0.001), pyruvate (1.3 ± 0.3 vs. 0.7 ± 0.1 μmol/L, p = 0.005), glucose (3.9 ± 0.9 vs. 1.6 ± 0.6 μmol/L, p = 0.007), and acetoacetate (0.7 ± 0.1 vs. 0.4 ± 0.1 μmol/L, p = 0.009) release in bile on reperfusion compared to I/R. Glycine induced a reduction of liver I/R results in increased bile flow and altered bile composition.