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Concanavalin A (ConA) induces natural killer T (NKT) cell-mediated liver damage. Glucocerebroside (GC) is a naturally occurring glycolipid. Our aims were to determine the effect of GC in a murine model of ConA-induced hepatitis. Mice in groups A and B were treated with GC 2 h before and 2 h following administration of ConA, respectively; group C mice were treated with ConA; group D mice was treated with GC; group E mice did not receive any treatment. Liver damage was evaluated by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver histology. The immune effect of GC was determined by fluorescence-activated cell sorter analysis of intrahepatic and intrasplenic NKT lymphocytes, measurement of cytokine levels, and Western blot analysis for STAT 1, 4, 6, and NF-κB expression. The effect of GC on NKT cell proliferation was assessed in vitro. Serum AST and ALT levels were markedly reduced in GC-treated group A mice compared with nontreated group C animals, and histological damage was markedly attenuated in group A. The beneficial effect of GC was associated with a 20% decrease of intrahepatic NKT lymphocytes, significant lowering of serum IFN-γ levels, and decreased STAT1 and STAT6 expression. In vitro administration of GC led to a 42% decrease of NKT cell proliferation in the presence of dendritic cells but not in their absence. Intraperitoneally administered radioactive GC was detected in the liver and bowel. Administration of GC led to amelioration of ConA hepatitis associated with an inhibitory effect on NKT lymphocytes. GC holds promise as a new immune-modulatory agent.

Background Ischemia and subsequent reperfusion (IR) may induce local and remote organ reperfusion injury. It may be propagated by xanthine oxidase (XO)-generated oxidant stress. We investigated whether pancreas IR directly and acutely induces renal dysfunction and if this outcome could be prevented by mannitol. Materials and Methods Rat pancreases were isolated and perfused with Krebs-Henseleit solution enriched with 5% bovine albumin. Other rats donated kidneys that were perfused at constant pressure mode. Each pancreas underwent 45 min of either perfusion (control) or ischemia (no flow). Both organ perfusion systems were then combined and the kidneys were perfused with the pancreatic 15-min reperfusate for 2 h. A third group consisted of paired ischemic pancreases and nonischemic kidneys treated with mannitol 250 mg/kg body weight during reperfusion. Results The controls demonstrated no abnormal perfusion or metabolite changes. Pancreas and renal perfusion pressures increased by >50% in the ischemia group immediately upon reperfusion; it remained above the values of controls during the 2-h kidney reperfusion. Conversely, perfusion pressure in the treatment group was not significantly different from the control. The reduced glutathione level increased significantly, as did XO, immediately upon starting reperfusion in both organs appertaining to the ischemic group; this misbalance was not documented in the controls and the mannitol-treated groups. Urine output was severely reduced in the IR kidneys. Conclusion Ischemia/reperfusion of the rat pancreas evokes immediate renal dysfunction. Kidney oxidant-antioxidant balance is disturbed, but can be prevented with mannitol. These two figures underline the role of oxidative stress in promoting acute renal damage in the presence of pancreas IR.