Protective effects of L-arginine on reperfusion injury after pancreaticoduodenal transplantation in rats

BACKGROUND: Post-transplantation pancreatitis andgraft thrombosis are two major complications of pancreastrans-plantation that contribute to morbidity, mortality, andgraft loss. Nitric oxide (NO) is a potent vasodilator agentformed when L-arginine ( L-Arg) is converted to L-citrul-line by the action of NO synthase (NOS), and plays a ma-jor role in microcirculatory changes. We therefore investi-gated the effect of L-Arg on reperfusion injury followingpancreaticoduodenal transplantation in rats.METHODS: The homologous male Wistar rat model ofheterotopic total pancreaticoduodenal transplantation wasused. The L-Arg-treated rats received the intravenous in-jection of L-Arg 5 minutes before and after reperfusion at adose of 200 mg/kg while the N-Nitro-L-arginine methyl es-ter (L-NAME) -treated rats at a dose of 10 mg/kg. Theamount of NO in the pancreas graft was measured. Serumconcentration of cytokine-induced neutrophil chemoattrac-tant ( CINC) was determined by enzyme-linked immu-nosorbant assay, the expression of CINC mRNA was detect-ed by Northern blot assay in the pancreas graft, and the ac-tivity of myeloperoxidase (MPO) was measured. Histolo-gical examination was performed.RESULTS: The amount of NO was higher in the L-Arggroup than in the control group, while it was lower in theL-NAME group than in the control group (P <0.05). Thepeak of serum CINC concentration occurred 3 hours afterreperfusion with the difference among the groups being sig-nificant. The expression peak of CINC mRNA in the pan-creas graft occurred 3 hours after reperfusion. The expres-sion level in the L-Arg group (7.66 ± 1.53 μg/L) was lowerthan in the control group (26.31±2.01 μg/L), while in theL-NAME group (34.18 ±3.12 μg/L) it was higher than thatin the control group (P <0. 05). The activity of MPO inthe L-Arg group was obviously decreasd as compared within the other groups. The pancreas inflammation was ame-liorated when L-Arg was administered, whereas the panc-reas damage was aggravated when L-NAME was adminis-tered.CONCLUSIONS: L-Arg can increase the amount of NOand inhibit the elevation of CINC, the CINC mRNA ex-pression and early neutrophil accumulation in the pancreas.NO has protective effects on ischemia/reperfusion injury inpancreaticoduodenal transplantation.