Protective Role of Nitric Oxide in Ischemia and Reperfusion Injury of the Liver

Abstract

Background: The suppressed production of nitric oxide (NO), associated with endothelial dysfunction, is thought to be a cause of ischemia and reperfusion injury of the liver. But findings of the salutary effects of NO enhancement on such injury have been conflicting. In this study, we tested our hypothesis that NO enhancement would attenuate ischemic liver injury. For this purpose, an NO precursor, L-arginine, and a novel NO donor, FK409, were applied to a 2-hour total hepatic vascular exclusion model in dogs.

Pharmacological Preconditioning Using Intraportal Infusion of L-Arginine Protects Against Hepatic Ischemia Reperfusion Injury

“…Consistent with prior reports [4,33,34], we observed greater sinusoidal congestion and a greater presence of PMNs in the non-preconditioned group. Necrosis, on the other hand, was similar between groups.…”

“…The significant reduction of AST levels measured 3 hours after reperfusion reflected the beneficial effects of preconditioning treatment in this in vivo I/RI model, which is consistent with previous studies [6,13,17,33,34]. The serum level of AST was distinctly elevated in both groups subjected to I/RI.…”

“…Peroxynitrite, a highly reactive species generated when excess NO reacts with superoxide [7,21], does not appear to have been significantly generated. This hypothesis is based on the beneficial results of this study and supported by previous studies showing that, even with high dose blood infusions (100 mg/kg-600 mg/kg) of Larginine, relatively low quantities of NO are produced during the early phase of reperfusion [12,17,34,52].…”

“…Maintaining serum NO levels during reperfusion by L-arginine administration has also demonstrated a protection effect through reduced oxidative stress and diminished lipid peroxidation [19,[33][34][35]. In this study, the serum levels obtained from TBARS were higher in the non-preconditioned group than in other groups in practically all collected samples, but the values obtained were not statistically significant.…”

Rb1 postconditioning attenuates liver warm ischemia–reperfusion injury through ROS-NO-HIF pathway

“…In the current study, we found that Rb1 post-treatment significantly reduced hepatic ICAM-1 mRNA levels during early reperfusion periods, and suppressed neutrophil accumulation in liver. These findings are consistent with previous reports that inhibition of NO synthesis increased ICAM-1 expression and enhanced neutrophildependent reperfusion injury in hepatic warm I/R injury (Liu et al, 1998) and that NO enhancement attenuated neutrophil infiltration and hepatic warm I/R injury (Shimamura et al, 1999). Therefore, upregulated NO by Rb1 post-treatment might also have a role in modulating the inflammatory process by decreasing the expression of TNF-α and ICAM-1.…”