Beneficial Effects of Fk409, a Novel Nitric Oxide Donor, on Reperfusion Injury of Rat Liver

Abstract

FK treatment in the immediate reperfusion period improves hepatic microcirculation and confers a significant protective effect on hepatic ischemia-reperfusion injury in the rat.

L-Arginine, but Not L-Name Protects Against Liver Injury Induced by Experimental Ischemia-Reperfusion

“…This value has not changed significantly in the liver relative to the control group of similar animals. The level of NO 3 -in the blood did not change significantly compared to the liver where it was reduced by 65.5 % (Table 3). Quantitative indicators can be evaluated as a manifestation of a decrease in the total content of final metabolites of NO in both blood and liver during I/R trial.…”

“…According to some studies the application of NO precursors minimizes the adverse effects of reperfusion and improves hepatic microcirculation [3,4]. On the other hand, studies of some researchers suggest that inhibitors of NO synthesis can prevent liver damage during I/R [5].…”

Blockade of the l-arginine/NO synthase pathway worsens hepatic apoptosis and liver transplant preservation injury

“…43 To determine whether an NO donor could ameliorate the liver graft injury, we performed a pilot experiment with the systemic NO donor FK409. 16 Apoptosis in the liver grafts was partially ameliorated by TUNEL assay (data not shown). Serum transaminase release was not significantly influenced, although this may be a dose-dependent phenomenon recognizing the limitations for use of systemic NO donors with potential for hypotension.…”

“…Others have shown a beneficial role for NO donors for both warm liver ischemia/reperfusion injury and in the transplant setting. 11,16,43 While it is clear that nonselective NOS inhibition is detrimental to the liver graft, the exact role of iNOS protein expression in preservation injury has yet to be elucidated. In all groups, iNOS protein expression peaked in the liver graft 6 to 12 hours after reperfusion.…”

“…[11][12][13] Other studies in rodent, canine, and porcine models have shown that the administration of NO donors or supplementation of the NO precursor (L-arginine) attenuated warm ischemia/ reperfusion injury. [14][15][16][17][18][19] NO protects the liver by improving microcirculation through vasodilation and antiplatelet effects, inhibiting neutrophil activation, neutralizing toxic free radicals, and exerting antiapoptotic effects. However, excessive NO production from induced NOS could exert cytotoxic effects on the liver.…”